for mediasti- nal ânullâ-cell lymphoma: 6 of 12 of the patients of Levitt and ..... Zola. H, Bor- rasca. AL: Immunological phenotype of neoplasms involving the B.
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
1987 69: 1087-1095
Mediastinal lymphoma of clear cell type is a tumor corresponding to terminal steps of B cell differentiation P Moller, G Moldenhauer, F Momburg, B Lammler, M Eberlein-Gonska, S Kiesel and B Dorken
Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
Mediastinal
Lymphoma Terminal By Peter
M#{246}Iler,Gerhard Maria
This
article
ring
in young
reports
predominantly badly
noted
and
in one
The
growth ever,
be
In
highly
tion
and
clear
carry stages
immunoglobulin of
the
HLA-D,
and surface such
expressed,
neoplastic
the
frequently
than
so-called
Ig
Ig constituents Ig deficiency,
from
deviant
that
they
kin’s (“T
cell,
convoluted”
Hodgkin’s thymic
is reported
and
carcinoma,
and
T cell
to
colleagues,23
(Mohri,24
rarely
50 cases)
148
cases)
tumors
of proven
B cell
reports
on primary
extranodal
to
origin.
non-Hodgkin’s
such
presenting
obstruction
as
originating
organs
cough,
in
and
antineoplastic
and
treatment.
as
rosis was
described
Concerning were able
to prove
dyspnea,
The
mediastinum
structures
described differentiated,
pain,
symptoms.
initial the
chest
tended
in most cases As to morphology,
are
of the
three
medias-
and
venous
tumors apparently to invade adjacent responded badly to the tumors were
being of diffuse large cell type or as poorly lymphocytic. In one series,27 pronounced sclethe
as an
additional
immunophenotype,
the “lymphoreticular
Blood, Vol 69. No 4 (April), 1987:
pp
characteristic
feature.
Perrone and colleagues27 origin” of 53 of their
1087-1095
type
of
B cell
of
B cell
terminal
steps
lym-
a mixture
of monoclonal
surface
that
these
of B cell origin although characterized late
stage
of B cell
29.4 years)
METHODS
B symptoms
female
of thoracic were
noted
lympho-
maturation. AND
predominantly
consisted
avail-
formalin-fixed
“null”-cell
the last 2 years, eight were observed. They occurred
symptoms
techniques using
present an immunophenotype by various defects, is indicative
During
tumors
pnea;
marker or by
mediastinal
and
MATERIALS
tinal
described by the three groups however, neither as B nor
of publication
we report
ic
primary
in young
thoracic I case.
medias-
( I 9 to 43 years,
(6 of 8) adults.
pain, in only
unusual
First
clinical
venectasia, Tumor
and dys-
localization
was
as mediastinal in 6 and as (para-)thymic in 2 cases. Initial diagnosis revealed involvement of the lungs in 3, of the pericardium in 2, and of cervical lymph nodes in I case; venous compression or invasion was observed in 3 patients. None was initially leukemic or developed leukemia. Serum electrophoreses were normal. The clinical course was characterized by therapeutic failure. Even though aggressive protocols against high-grade malignant lymphomas were
lymphomas
and poor prognohave a number of mostly young female
with pronounced aggressiveness Conspicuously, these lymphomas features in common: The patients were
tinum2527
adults
as by
however, Tubbs and (Bernard
there
sis.
undescribed
applying
by
using
time
Patients.
mediastinal
lymphoma
cell
described
Collins’8),
(reviewed
Nevertheless,
clini-
clear
Inc.
are
mas
mean
Hodg-
lymphomas
material. Here
detect-
primary
and
mediastinal
the
& Stratton,
tumors
at the
to lack
B cell
contain
able
that,
sarcoma
to
and
antibodies to leukocyte common (LC) antigen on paraffin sections. Furthermore, immunoreactivity with antisera to and A light chains suggested a B cell origin of five of these
of a very
and
the
is a previously
by Grune
even
malignomas of
and
fail
of
mediastinum is T cell tumors
Lukes
epithelial
a 1987
acute
lymphomas,’2’5
of immunophenotypical that
corresponding
orjgiflSO;
Otto20). Even large series of malignant lymphomas, (eg, Brittinger and colleagues,2’ 1,127 cases; colleagues,22 564 cases), of mediastinal lymphomas and
most
percentage of cases.” Apart of B cell tumors may be in physiologic development
according
disease,’9
In may
common
carcinoma.’7 The site of lymphoblastic
primary
to be the
known
and of B cell
mimic
and even
amounts. since
variable
HLA-DR
differentiation.
as T cell
antigen4
expression
actually
a small
occasionally
disease,’6
large Ig
and
B cell-restricted/associated
tumors. The remaining tumors of authors could be characterized,
cell-associated
lymphomas
cytomorphology that of B cells
from
differentiaby Nadler’) and
assumed
leukemia in
in
exhibited
HLA-A,B,C
of other
combination
60 mediastinal
histo-
I (1-ILA-
and the TlO
initially
are
lym-
lymphoma
(surface/cytoplasm). cells
LC,
major
class
plasma
deficient
“null”-cell
B lymphocytic
able
of
is secreted
leukemias
B cell was
express
PCA-l,2’3
however,
lymphoblastic chronic
as
surface. At the terminal differentiation antigens,
Ig disappear;
PC-l,
as the
and B cells,
more
occur
on their B cell
size.
of
suggests
(MCCL)
Ig
,
neoplastic
expression
This
features
phoma
how-
CD21 the
expression
antigens.
L#{227}mmler,
CD2O,
in the
to
D#{246}rken
In addition,
inconstant cal
a diffuse
immunophenotype
B cells
leuke-
could,
PC-i
defects
is pres-
of variable but
antigens
(Ig)
differentiation,
antigens are
cells
histologically.
the
patients
had
class II (HLA-D), lineage-restricted CDI9, CD2O, CD22 (reviewed
antigens
.
developed
characterized
cases.
CD19,
and
Corresponding
Birgit
Bernd
cALLa.
proliferative,
comprised
and
occur-
1 0, 1 1 , 1 3. 18,
died
Momburg,
years),
Progression
patients
Frank Kiesel,
29.4 Most
No patient
ORMAL PERIPHERAL compatibility (MHC)
A,B,C)
so
five
be classified
all
adults.
Sophie
tumors
mean
therapy.
immunohistologically
phomas.
N
and
not
years.
eight)
diagnosis.
Moldenhauer,
Eberlein-Gonska,
mediastinal
43
of
patient; were
pattern, could
(six
after
tumors
They
to
to aggressive
22 months
mia.
primary
(19
female
responded ently
eight
adults
of Clear Cell Type is a Tumor Steps of B Cell Differentiation
From
the
Medicine, ogy
Institute
and
July
Supported
by the
Baden-
and
ofHeidelberg:
Genetics,
FRG. Submitted Land
ofPathology
University
German
Cancer
14, /986;
accepted
Tumorzentrum
Wurttemberg
the
and
Department
of Internal
the
Instituzefor
Immunol-
Research
Center,
Heidelberg,
November
1, 1986.
Heidelberg/Mannheim (Forsch
and
the
ungsschwerpunkiprogramm
17.9).
Address gisches 220,
reprint
Inslitut D-6900
requests
der
to PD Dr med
Heidelberg,
The
publication
costs
ofthis
article
payment.
This
article
must
“advertisement”
Mbller,
Im
Neuenheimer
in
PatholoFeld
FRG.
charge indicate
Peter
Universit#{228}t Heidelberg,
accordance
with
were
defrayed
therefore 18
U.S.C.
in part
be hereby §1 734
by page
marked solely
to
this fact.
© /987 by Grune & Stratton, 0006-4971/87/6904-0019$3.OO/O
Inc.
1087
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MOLLER
1088
Table Age
Case Patient
1
B.M.
Data
at
Clinical
Diagnosis
No.
1 . Clinical
Sex
lyears)
F
19
First Clinical Symptoms
Left breast facial
Primary Localization
venectasies;
Preliminary
Cell Morphology Tumor
(Para-)
edema
Large,
Diagnosis
polymorphic
Hodgkin’s
thymic
disease
Radiation
F
2 1
B-symptoms: night weight
3
WI.
F
3 1
Mediastinum
fever,
Large,
polymorphic
Malignant
sweats,
lym-
liver infiltrations
abdominal
loss
Thoracic
phoma
pain (left);
Mediastinum
Large
dry cough
and medium-
sized,
Malignant
poly-
lymphoma
morphic
4
LI.
F
35
Painful
right
thorax; G.S.
F
35
Mediastinum
Relatively
moderate
dyspnea 5
shoulder/
Thoracic
monomorphic
lym-
5.5.
F
43
Thoracic with
Mediastinum
Medium-sized relatively
on exertion
to
Thymoma
small,
piratory after
M
monomorphic
venectasies
Mediastinum
found
effusion
death
insufficiency
due to rae1 1 months
diagnosis
Local progression;
abdominal
lymph
involvement
node
Local proession;
Malignant
monomorphic
lymphoma
enlargement
Mediastinum
Medium-sized,
in a routine
lung involvement; lymphomas;
due to respiratory
Medium-sized,
cervical
Mediastinal
22
10 months lung involve-
and pericardic
retroperitoneal
intumescence KM.
7
death with
progression;
12 months
6
after diagnosis
progression;
ment
tracheo-
pneumonia;
fistula;
22 months
after diagnosis Local
and
lymphomas;
phoma
dry
moderate
dyspnea
Malignant
on exertion pain,
cough,
small,
Local
Intervention,
and Chemotherapy
Progression;
death
F.M.
Course
After Surgical
esophageal
2
ET AL
Hodgkin’s
polymorphic
disease
piratory after
diagnosis
after
Local pro’ession;
death
insufficiency death
insufficiency
due to res18 months
diagnosis
Presently
in complete
after combination
remission chemotherapy
X-ray 8
5G.
M
29
Cervical
swelling;
facial
and brachial
Do ne on th e basi s of routine applied
in 7 cases,
remission
hematoxylin was
achieved
(Pare-)
edema
and eosin in only
Medium-sized,
thymic
sect ions for rapid 1 case
(patient
7,
who received combination chemotherapy comprising endoxan, holoxan, vincristine, and prednisone [CHOP]). Five patients died I 0, 1 1 , I 3, 18 and 22 months after initial diagnosis of extensive disease and large thoracic tumor masses causing respiratory insufficiency (Table I). Tumor tissue. Fresh tissue was transferred to our laboratory immediately after surgical removal. Representative samples were quick-frozen
in liquid
nitrogen.
Frozen
sections
(4
to 6 Mm)
were
fixed in acetone for 10 minutes at room temperature, and immunostained immediately or stored at - 20#{176}C for I to 3 weeks. Another sample was fixed in Bouin’s fixative for routine processing purposes; histochemical stains from the paraffin-embedded material were achieved by using hematoxylin and eosin (H & E), periodic-acid Schiff’s (PAS), Giemsa, and the Gom#{246}rireticulin method; immunostaining of paraffin sections was preceded by bleaching and destruction of endogenous peroxidase by methanol/ H2O2. Reagents. Monoclonal antibodies (MAbs) to 1gM (R1/69) and IgD (IgD26), to the leukocyte common antigen (2Bl I and PD7/26), and anti-Ki-I were obtained from Dakopatts, Copenhagen. MAbs against the T4 antigen (anti-Leu-3a (5K2)), the T8 antigen (antiLeu-2b (SK3)), (163-42) and A (1-155-2) light chains, to the interleukin-2 (1L2) receptor (2A3) and the CD22 antibody antiLeu- I 4 were purchased from Becton Dickinson, Mountain View, CA. MAbs to the TI I , T6, and T3 antigens were obtained from New England Nuclear, Seattle (Lyt3) and Ortho Diagnostics, Raritan, Ni (OKT6, OKT3), respectively. MAbs to common-ALL antigen (cALLa) (J5), to the B cell antigens CD2O (BI), CD2I (B2), CDI9 (B4), and mAbs PC-I and PCA-l, both directed against plasma air-dried
overnight,
cell-associated Hialeah,
FL.
antigens, MAbs
were
specific
furnished to framework
by
Coulter determinants
Immunology, of
HLA-
Malignant
monomorphic
Pro’ession;
liver,
lym-
adrenal
gland
phoma
lymphomas
kidney, infiltrations;
and cervical
notification.
(W6/32) B cell activation
HLA-DR (2.06), and Blast-2, reacting with a (CD23 antigen) were generous gifts from the producing laboratories (given in references in Table 2); the B cell reagents HD6, HD28, HD37, HD237, HD39, and HD5O are products of some of us (B.D., G.M., 5K.), as is the antibody HEA I 25 that reacts with a surface glycoprotein (Egp34) restricted to normal and neoplastic epithelial cells (G.M., F.M.). A polyclonal biotinylated sheep antibody to mouse Ig and a streptavidin-biotinylated peroxidase complex, both obtained from Amersham Buchler, Braunschweig, FRG, served as detection system for the monoclonal primary antibodies. Unconjugated rabbitderived antisera to human -, a-, -, ic-, and A-chains, swine anti-rabbit Ig serum and peroxidase-rabbit antiperoxidase complex were purchased from Dakopatts. Anti-human 6-chain and i-chain sera were obtained from Nordic Immunology, Tilburg, Netherlands. Pooled human lgG (Gamma-Venin) was supplied by Behringwerke, Frankfurt, FRG, 3-amino-9-ethyl carbazole (AEC) and N’Ndimethylformamide (DMF) were obtained from Sigma, St Louis. Staining procedures. MAbs in culture supernatants were used undiluted; ascites preparations were used as 1 :200 dilutions. The anti-mouse Ig antibody was diluted I :50, and the streptavidinperoxidase complex was diluted 1: I 00. Dilutions of primary antisera ranged from I :50 to I : I 500; the anti-rabbit Ig antiserum was diluted I :20, and the peroxidase-antiperoxidase complex was diluted 1:100. All dilutions and washing steps were carried out in phosphatebuffered saline (PBS); the secondary antibody solution contained 5% pooled human IgG to inhibit cross-reactions with human surface 1g. Incubation times of tissues were I hour at room temperature for the primary antibody (respective antiserum) and 30 minutes for the second-step and third-step reagents. Using AEC as the chromogen (0.4 mg/mL in 0.1 mol/L of acetate buffer pH 5.0 with 5% DMF and 0.01% H202 for 10 minutes), the peroxidase reaction resulted in A,B,C
and
antigen
rny-,
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MCCL
OF B CELL
TYPE
1089
Table
2.
Antigens
Detected
Antigen
an d Primary
Antibodies
MW KD
Used
in This
Study
Clone
Source
(Reference)
MHC B. C
HLA-A, HLA-DR
B cell-associated
12;45
W6/32
Barnstable
29;34
2.06
Charron
and McDevitt
et al (28)
Warnke
et al (30)
Leukocyte
common
cALLa(CD1O) B cell-restricted
200
PD7/26,
100
J5
Ritzetal(31)
2B 1 1
HD37
Pezzutto
B4
Nadleretal(33)
antigens
CD 19
95
CD 20
et al (32)
35 140
B1
Stashenko
CD21
B2
Nadleretal(35)
CD 22
135
HD6
Moldenhauer
HD39
Darken
Leul4
Schwarting
Blast-2
Thorley-Lawson
HD5O
(author’s
laboratory) et al (2)
CD 23 Plasma
45
cell-associated
et al (34) et al (36)
et al (37) et al (38) et al (39)
antigens
Plasma-cell
antigen
28
PC- 1
Anderson
Plasma-cell
antigen
24
PCA-1
Anderson
antigen
45
OKT1O
Reinherz
antigen
1 16/126
Ki-1
Stein
lL2 receptor
60
2A3
Pali et al (unpublished
T10
(29)
antigens
et al (3) et al (4)
Varia Ki-1
et aI (40)
(Becton
observations)
Dickinson)
T cell antigens Til
55
9.6
Kamounetal(41)
T6
49
OKT6
Reinherz
et al (4)
T3
19
OKT3
Reinherz
et al (42)
T4
55
SK2
Evansetal(43)
32;43
SK3
Evans
HEA125
Momberg
T8 Epithelial
Egp34 MHC.
major
34 histocompatibility
using
paraffin
negative method. MHC and
result Intrinsic antibodies
macrophages
on
and the
No staining
controls interstitial
that,
by their
reaction and thus controls were performed rum).
sections tissue
were
the
gled granulocytes was not destroyed.
frozen tumor
positive
was
from was
for
the
staining,
cells, indicated
except
sections
the
to ensure
and
not
that
due
primary for the
whose
antibody reaction
a
cells,
reliability
results.
endogenous
of
Negative (antiseof intermin-
(Fig
as
The
large
as the
further
lin fiber
characterized scaffold;
case
by an alveolar I showed
a diffuse abundant
even resembled Hodgkin’s immunophenotype.
Reed-
Sternberg cells. The nucleoli were predominantly small and mostly singular. In cases I and 2, the tumor cells are best described as large and pleomorphic; in case 3 as mixed, large
peripheral
histologic
picture
to microalveolar reticupronounced sclerosis. In
the
pleomorphic
resembling
monomorphic. twice
with any of the morphologically defined B cell listed in the current classifications. The histoof these lymphomas resembles either pleomor-
cells
nuclei
but
were
compatible lymphomas morphology
but varied considerably in size. The to very irregular; one tumor contained nuclei, and a second revealed giant
extremely
small
however,
conclusion,
cytoplasm in common nuclei were roundish cells with multilobated with
relatively
cells,
diffusely infiltrating normal lymphocytes that were a regular constituent of the lesion. Tumor necroses, mostly ill-defined and small but never confluent, were observed in six cases. Mitoses were numerous and always typical. Even more frequent were single-cell degenerations. The tumors were
phic
Most of the tumors showed 1). The cells had clear and
to tumor
6 and 8 as 1) as mixed,
peroxidase
RESULTS
Histomorphology. growth pattern
medium-sized smallest
of the
endothelial the
and medium-sized and pleomorphic; in cases medium-sized monomorphic; and in case 5 (Fig
to the
immunoreactivity
false-negative
by omitting observed,
tonsils
reliable
dendritic
excluded
in frozen
et al (44)
complex.
an intense red precipitate. The sections were counterstained with Harris’ hematoxylin and mounted with glycerol gelatin. Controls. To obtain reliable results, the detection of Ig components was performed twice, using antisera on paraffin sections and mAbs on frozen sections. Positive controls were made at the same time,
et al (43)
antigen
T cell lymphoma
of these
tumors
or thymoma;
disease. (Table 3)
The
was
not
in two cases,
tumors
were
it
LC
and HEA125 and thus clearly defined as nonepithelial in nature. They all expressed the B cell-restricted antigens CDI9 and CD2O, as could be shown by the binding of mAbs HD37, mAbs cases; expressed
HD237,
B4,
and
BI,
showed minor differences B4 failed to react with on the tumor
cells
respectively.
The
first
three
in binding intensity in five tumors 3 and 7. CD22 was
of six cases
but was
undetectable
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MOLLER
1090
ET AL
in cases 3 and 8. CD23, a putative B cell activation antigen, was present on tumor cells ofcases I and 4 (Fig 2) and on a minor part of the neoplastic cells of cases 7 and 8. Two other activation antigens, Ki-l and the IL 2 receptor, could not be detected. chains,
Immunoglobulin constituents (heavy and J chain) were not detectable in the whole tumor
in either
the cytoplasm
or on the surface
of various light and heavy chain mature, morphologically typical ever, were very scarce. minute islands of small, surface
1gM
(Fig
3).
In
addition, one round lymphoid
The
Ig
neoplastic
case contained cells carrying
cells
of
every
case
bound
population and in a varying number 2, and 4. MAb OKTIO, also known reacted
population detected cies
cells.
was present only in cells, which, how-
PC- I , a mAb recognizing a plasma cellantigen (Fig 4). PCA-l, another mAb of this reacted in cases 5 and 6 with the entire neoplastic
strongly associated category,
cells,
of the tumor
classes plasma
light series
with
tumor
2 and
of tumor cells of cases I, to bind to normal plasma
with
parts
of the
neoplastic
of case 4 CALLA and CD2I could not be in either case. The tumors showed variable deficienMHC antigen expression: at least two cases com-
in
pletely lacked class I and class II antigens (Fig 5); a third case (case 6) contained only a very small number of scattered HLA-ABC
Fig 1 . Primary mediastinal clear cell lymphoma of B cell type: Case 5. Predominantly medium-sized tumor cells with very pale cytoplasm and roundish nuclei, diffuse growth pattern. Arrow: vessel surrounded by normal peripheral (T) lymphocytes. Hematoxylin and eosin; original magnification x 140.
origin,
3.
Antigen-Expre
ssion
of Tumor
Cell s in Eight
HLA-DR
cells
large
cells
(Fig 6); although be completely ruled
it cannot
among
probably out that
the of those
unreachistiocytic cells were
part of the neoplastic population. Four other tumors tamed varying proportions of MI-IC antigen-deficient plastic
Table
and
tumor
tive
Cases
cells.
The
coordinate
of lg-Mediastinal
Clear
expression
Cell Lympho
ofclass
I and
conneoclass
II
ma of B Ce II Type
Patient
Clone
Antigen
1, B.M.
2, F.M.
3, WI.
4, LI.
W6/32
-
+
-
HLA-DR
2.06
±
+
-
LC
PD7/26and
+
+
+
+
+
2B1
CALLA(CD
10)
CD19
± +>-
6, S.S.
5, G.S.
HLA-ABC
-
>
-
+
8, S.G.
-
±
-
+
+
+
+
->>+
+>-
7, KM.
1
J5
-
-
-
-
-
-
-
-
HD37
+
+
(+)
+
+
+
+
(+)
HD237
+
+
+
(+)
+
-
(+)
(+)
+
±
+
84
+
+
-
+
CD2O
Bi
+
+
+
+
+
+
+
CD21
B2
-
-
-
-
-
-
-
-
CD22
HD6
+
+
-
+
(+)
+
+
-
+
-
CD23
Plasma
cell-associated
antigen
antigen
lL2receptor T cell antigens
T6. Ti 1, T3, T4, T8
+
HD39
+
+
-
+
+
+
Leul4
+
+
-
+
+
+
Blast-2
+
-
-
+
-
-
±
±
HD5O
+
-
-
+
-
-
-
-
PC- 1
+
+
+
+
+
+
+
+
PCA-1
+
-
-
->>+
-
-
-
-
OKT1O
-
+
-
->+
-
-
-
-
-
-
-
-
-
-
-
-
Ki-1
-
-
-
-
-
-
-
-
2A3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
Ig (cytoplasmic/surface) Ki-1
(+)
OKT6,
Lyt3,
OKT3.
(+)
-
Leu3a,
Leu2b Egp34
.
-
,
HEA125 Negative;
+
,
positive
negative tumor cells clearly
reaction outnumber
on the entire positive
ones;
-
tumor -
-
cell population; >>
+ , very
(+
-
),
few scattered
weakly
positive
-
-
positive; cells,
±
, positive
putative
and negative tumor
cells.
-
tumor
-
cells in equal
-
parts,
+,
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MCCL
OF B CELL
TYPE
1091
Fig 2. Case 4. Monoclonal the activation-associated CD23 to the
tumor
of the x122.
cell
population
lymphoma.
but
antibody antigen not
Immunoperoxidase;
(MAb) HD5O recognizing bound in varying intensity
to the
stromal
original
cell
component
magnification
Fig 4. Case 8. Monclonal plasma cell-associated antigen cell
population.
Negative
Immunoperoxidase;
antibody (MAb) bound strongly
connective
original
tissue
magnification
PC-i recognizing a to the entire tumor fibers
are
Fig 3. Case 2. Demonstration of 1gM by monoclonal antibody (MAb) Ri /69. The large tumor cells were devoid of detectable 1gM whereas scattered reactive small lymphocytes stained strongly. thus excluding a false-negative result. Immunoperoxidase; original
Fig 5. Case 5. Monoclonel antibody (MAb) W6/32 stained dendritic interstitial cells and small infiltrating cytes but did not bind to the tumor cell population. thus
magnification
original
x 305.
its
abnormal
loss
magnification
of
HLA-A.B,C
x 122.
molecules.
apparent.
x 133.
strongly Iymphoindicating
Immunoperoxidase;
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
1092
MOLLER
involvement
of pericardium
the patients Trump and involvement
aggressive
involvement
in Perrone’s
antineoplastic and
sion,
but
in three
of
and Mann’s group, and 3 times in our The chest wall was the most frequent site
of extrathoracic
of our patient
examination
of Levitt and colleagues, I of the patients of Mann, and in 2 of the patients of our series; lung was noted twice in Levitt and colleagues’ group,
3 times in Trump group of patients.
Levitt
at initial
ET AL
colleagues
neither
series.
treatment, reached
of Trump
a transient
and
patients was regarded developed leukemia.
When
10 of the
Mann’s
given
patients
complete
patients
of remis-
and
only
one
as disease-free afterwards. Progressive disease, relapse,
No and
chemotherapeutic failure was commonly noted. Four of the patients of Levitt and colleagues, 8 of Trump and Mann’s, 20 of the patients of Perrone and colleagues, and 5 of our patients were dead at time of publication, with a survival time
ranging
Trump we are
from
clinical
cells
but
stained
interstitial
antibody failed
dendritic
(MAb) 2.06 recognizing a to react with the tumor
cells
and
a small
of large scattered cells. most probably of histiocytic noperoxidase; original magnification x 195.
antigens cell
was
small
T6,
lymphoid
the
tumor
vessels
only in case
noticed
antigens
TI I, T3, cells
cells (Fig
I).
series
is characterized expression, by the
, CD2
CD20 ing
that
various
of
case. eight
and
represent
tumors
with
around blood mAb HEAI25
polymorphic
complete
against T stained
amounts
by variable defects constant phenotype
I , PC- I
they
in
Immu-
mediastinal
in MHC CDIO,
CD19,
differentiation.
aspects,
the clinical
non-Hodgkin’s
resemble
those
colleagues,25 leagues.27
As
of
Brittinger
and
there
seems
nal
“null”-cell
and
colleagues,
the
patients
has
to be a clear
ratio female
Levitt
and
male
predominance
to females
predominance
(eg, 9:1),
for mediasti-
lymphoma: 6 of 12 of the patients of Levitt 7 of I I of the patients of Trump and Mann,
mediastinal
mass,
,
cell phenotype never plasmocytic. neoplastic hairy cell
(Ku
T cell
,
antigens),
and Nine
colleagues and 6 of 8 of those of Levitt and and 85%
7 of our
patients of Perrone and
there
was
chest initial
additional
by
common
to all the
a terminal B cell differentiaby the presence of the plasma in 8 of 8, PCA-1 in 5 of 8, and that at least a partial plasma
is expressed although On the basis of the
cells, Anderson leukemia as a
and tumor
Plasmacytoma, plasma cell reported to express PCA-I
cytomorphology PCA-1 reactivity
is of
co-workers45 characterize of the pre-plasma cell.
leukemia, and myeloma PC-I ,2 and (OK)Tl0.’47
are On
other hand, the diffuse large cell lymphomas of B cell analyzed by Freedmann and co-workers48 failed to express PCA- I and PC-I , a finding that caused them to argue that these tumors are the neoplastic counterparts of normal B cells at the midstage of differentiation. Based on type
of cell
Perrone and colT lymphoblastic
group were aged s35 years. Cough, and venous obstruction were common from
with
mediastinum by
of males
colleagues, 8 of Trump and Mann’s, were younger adults ( 1 9 to 37 years);
Apart
patients
the
described
pronounced
colleagues,2’
43 of 60 of the patients of Perrone of those in our series were female.
colleagues’ dyspnea,
ofour of
Trump and Mann,26 and compared with mediastinal
which
lymphoma,
features
lymphoma
given
are B cell lymphoscheme given by CDIO, CD19,
observations
the
immunophenotype
of the
lymphomas described herein indicates that novel B lymphoma type. It might be placed
DISCUSSION
In several
CD2I
these tumors differentiation LC,
tumors of our series, suggests tion. This view is supported
these
primary
survival
the
antigen
Ig deficiency, suggestterminal B lymphocyte
of
CD20,
finding is that to the B cell immunophenotype
cell-associated antigens PC-I TI0 in 2 of 8 tumors, indicating
directed exclusively
T8
occasionally crowded epithelium-specific
in neither
tumors
2. MAbs
and
interspersed
and The
showed reactivity In sum, this
T4,
proportion
origin.
median
To conclude, we feel that type with a rather distinct
picture.
Our central mas. Referring Nadler,’ the Fig 6. Case 6. Monoclonal HLA-DR framework determinant
4 to 22 months;
and Mann was 16 months. dealing with a lymphoma
midstage
differentation
tumors.
regarded
This
cell
as the malignant
alternative cell,
and
tumor
pathway
also
known
counterpart
which
morphology
and
observations). Nevertheless,
plete
pain, signs.
(discussed unknown
tumor
express
loss
of
of Ig
CD22
alternatively
that
PCA-l
(P.
with
the
has
been
observed
to occur origin. antigen,
of an B
“immature cannot
differentiation that monocytoid are
be
stage
the monocytoid
so-called
sinus
be located
M#{246}ller,unpublished normal
mature
by
several
B cell,
lacks in This comauthors
in large cell B lymphomas Two of our tumors failed
as could
in
scheme. In this B cells have clear
MCCL exhibit considerable There are no Ig constituents.
previously) or follicular the
of the
as compared
the tumor cells antigen expression.
leukemia/plasma
of the final
is a B cell
current physiological context, it is noteworthy the
cell
cell might
of B cell development: as the cell
histiocytosis,”4952
hairy
variant
aleukemic
it is probably a between tumors
be verified
by staining
of to
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MCCL
OF B CELL
with
three
ways.
1093
different
CD22
defect
TYPE
mAbs.
expression
in gene
This
may
expression
may
either or
differentiation.
Furthermore,
ularities
in the
of
defect
or
affinity CD23
of the
of eight defects,
is
epitope
expression
of the CD23
of MHC class tumors but one. describing lack
in malignant
lymphoma:
observed this lack in three lymphomas, and the Daudi fl2-microglobulin,54 molecule. Because
to
within
DR
to a lesser the the
antigen
of functional be suspected because
must
several
irreg-
in six
nature. Severe of the partial or I molecule (HLATo our knowledge, of class I antigen
Woda
and
is part
of the
I antigens
ments of T cell-mediated cytotoxicity,55 HLA-A,B,C-deficient tumor cells possibly escape immune attack by cytotoxic T cells.56 This may account for the clinical aggressiveness of the
primary mediastinal Six of eight of the defects in expression
B cell lymphomas. tumors had either of the HLA-DR
probably
negative
2.06.
Our
were
evaluation
neoplastic
cells
partial or complete framework deter-
Defects
lymphomas
underestimates
the
the real population
were
as
by parallel
antigens. neoplastic
For multiple myeloma, plasma cells lost their
entering the terminal we discuss this stage down-regulation more unlikely
reactive
small
T cells,
with
it was class
as
mAbs
Although group,
neoplastic
of clear
a
seems loss, ie,
since all tumors I antigen-deficient.
for B cell activation63’65 expression
contribute B cells
might
of the
was
to T cell
assumed that the II antigens while
expression also class
transducers
by
of nonreactivity
intermingled
stained
a defective
molecules
lymphoma
noted for HLA-
stage of differentiation.4542 of development for our tumor
are Thus,
trigger
II antigen
of MHC class II antigen expression to us than assumption ofa pathological
II antigens
entiation
extent
since
regarded sections
in class
sporadically
of the staining
suggested
maturation.
class I ele-
as restriction
authors.57
Class
co-workers53
heterodimeric
serve
by mAb
in B cell
a further defect in antigen lacking class II molecules were
cases of large “histiocytic” B cell cell line is known to be devoid of
which class
recognized
expression
of
failed
or just
probably
complete nonexpression A,B,C) observed in all very few reports exist
minor
be answered. Because related to activation,39
nonexpression
tumors however,
a
course
HD237
minant
two by
cells of case 3; B4 did not this is due to inaccessibil-
corresponding
or complete
are
mAbs:
of these antibodies cannot antigen seems to be closely
partial
in
impaired
in the there
CDI9
react with a subset of neoplastic recognize tumors 3 and 7. Whether ity
interpreted
been
abrogated
terminal
binding
be
have
of these
and
important
to the incomplete differin the primary mediastinal
cell type. ACKNOWLEDGMENT
We are indebted to Dr H. Schmitteckert from the LVA-Klinik f#{252}r Thoraxkrankheiten (Heidelberg/Rohrbach) for supplying clinical data, to Ingeborg Brandt and iohn Moyers for technical assistance, and to Christine Raulfs and Hans-Ulrich Burkhardt for help in editing the manuscript.
REFERENCES I
.
Nadler
LM:
comments,
(eds):
B cell/leukemia
in Reinherz
Leukocyte
Typing
2. Anderson Nadler
KC,
LM:
normal
EL,
II. New
Bates
neoplastic
Nadler
Springer,
and
Bernstein
ID
reactivity
i Immunol
4.
Reinherz
EL, Kung
Discrete
of normal Proc
NatI
stages
PC, Goldstein
of human
restricted
132:3172,
G, Leven
intrathymic
to
RH,
Schlossman
differentiation:
thymocytes and leukemic lymphoblasts Acad Sci USA 77:158, 1980
7. Pelicci
cell”) their 8.
50:735,
Knowles PG.
L, Burke
F, Dalla-Favera
TM,
Identification
of two
ma. Lab Invest
A,
characterization panel
Mi,
major
51:504,
9. Al-Katib by a new
Hicks
R,
iS, Wang Wang
CY:
iolley
B cell
CS,
forms
Rangel
of nodular
JYM, S1g,
Bonetti E,
ML, Trela
(CLL)
leukaemia
3:261,
H, of the
Lab
Invest
Bj#{246}rkholm M,
HoIm
leukaemic
cell
in relation
to disease
G:
population
Surface in chronic
activity.
1-lema-
1985 BN,
Sheibani
K, Winberg
CD,
Burke
nuclei
iS, Rappain follicular
CR, Colby TV, Marty J: Multilobated of 7 cases. Hematol Oncol 3:79, 1985
Kjeldsberg
A study
I, Palutke M, Tabaczka P, Goldfarb S, EisenMSY: B-cell lymphomas morphologically resembling lymphomas. Cancer 56: 1578, I 985 Mirchandani
I 5. Parfrey NA, Mann nant large cell lymphoma Cancer55:19l3, 1985
determination 1985 CS,
Jones
mixed
origin.
of
tance
17.
RB, Selonick SE, Beschorner WE: of B-cell type with multilobated
Malignuclei.
Linch
DC, Jones HM, Berliner N, MacLennan K, O’Flynn ER, Kay LA, Goff K: Hodgkin-cell leukaemia of B-cell Lancet 1:78, 1985
antibodies.
Weiss
LM,
Warnke
Gatter
KC,
of analysing
immunohistological SE:
lympho-
Hematol
Oncol
R, Sklar
i: Most
HS:
Johnson Hodgkin’s
Alcock
C, Heryet
malignant techniques.
18. Lukes Ri, human malignant 19.
monoclonal
Mi,
T-cell
F,
(“null-
3:271, 1985
10. Cleary
neoplasms.
L, Pak
16.
1984
of
B lineage
port H: Neoplastic B cells with cerebriform lymphomas. Hum Pathol 16:173, 1985
14.
Wang CY, Bardales R, Koziner B: Phenotypic of “non-T, non-B” acute lymphoblastic leukemia (BL)
Mellstedt pattern
Nathwani
12.
are
K, Huehns
non-Hodgkin’s lymphomas. Multiparametric B- or T-cell lineage. Am J Pathol l 20:356, Grogan
lymphocytic
berg
1984
DM II, Dodson Flug
E,
immunoglobulin
lineage.
6. Gregg EO, Al-Saffar N, iones DB, Wright DH, Stevenson FK, Smith iL: Immunoglobulin negative follicle centre cell lymphoBr i Cancer
lymphomas
I 3. Weiss RL, B cell lymphomas.
Analysis
of T-cell
cell 1985
tol Oncol
1984
5. Horning Si, Doggett RS, Warnke RA, Dorfman RF, Cox RS, Levy R: Clinical relevance of immunologic phenotype in diffuse large cell lymphoma. Blood 63: 1 209, 1984
ma.
large
53:521,
I I . Kimby SF,
3. Anderson KC, Prak EK, Bates MP, Leonhard RCF, Schlossman SF, Nadler LM: Antigens on human plasma cells identified by monoclonal antibodies. J Immunol 130:1 132, 1983 SF:
null
1986, p 3 B, Schlossman
with
cells.
Summary LM,
Slaughenhoupt
antibody
plasma
workshop:
BF,
York,
MP,
A monoclonal
and
panel
Haynes
A, Mason DY: Clinical importumours of uncertain origin with Lancet I :1 302, 1985
Collins RD: Immunological lymphomas. Cancer 34:1488,
characterization
of
1974
DW, Hoppe RT, Cox RS, Rosenberg disease limited to intrathoracic sites.
SA, Kaplan Cancer 52:8,
I983 ,. 20. Otto HF: Pathologic Uhlinger E (eds): Spezielle Springer, 1984, p 227
des Thymus, pathologische
in Doerr Anatomic
W, Seifert G, Bd I 7. Berlin,
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MOLLER
1094
21.
Brittinger
prognostic
G,
the
relevance
lymphomas.
Results
lymphoma
the
Kid
study
group:
classification
of
non-Hodgkin
study
by the
of a prospective
multicenter
Clinical
and
22. Weick
disorders.
ative
Comprehensive
non-Hodgkin’s
ing formulation. 23.
Am
Bernard
Lemerle
Boumsell
and
24.
Mohri
Oncol
N:
13:591,
25.
Melvin
L: Non-T, with
B-cell
Li,
non-B
lymphomas
Trump
Aisenberg
DL,
lymphomas
with
subset
AC,
Perrone
RB:
lymphomas tumor.
Harris
are
Blood
J,
rare
in
59:549,
1982
Jpn
J Clin
origin.
NL,
Diffuse
with
patients
Linggood
lymphoma
RM,
of the
large
mediastinal
T, Frizzera
with
Pathol
cell and
undifferentiated
involvement.
non-Hodgkin’s
Pop-
mediastinum.
prog-
A poor
lymphoma.
Cancer
G, Rosai
diffuse
large-cell
sclerosis.
10:176,
Barnstable
J: Mediastinal
A clinicopathologic
study
of 60 cases.
Ci,
Bodmer
MP,
Brown
G, Galfre
G, Milstein
C,
antibodies
to
by two-dimensional
surface
anti-
of HLA-D-
gel electrophoresis.
J Exp
Med
l52:18s, 1980 30.
Warnke
Pulford
RA,
Gatter
K, Cordell
Diagnosis bodies.
of human N
31.
Falini
KC,
B, de WoIf-Peeters
lymphoma
with
Engl J Med 309:1275,
Ritz
J,
Modulation induced by
B, Hildreth
JL, Cohen
Pesando
JM,
of human monoclonal
P. Woolston
C, Mason
monoclonal
antileukocyte
Notis-McConarty
SF:
125:1506,
Pezzutto
A,
D#{246}rkenB, Feller
A, Moldenhauer
R, Wernet P, Thiel E, Hunstein W: HD37 useful reagent for further characterization phoid
malignancies,
1986,
p 590
33.
Nadler
LM,
iF, Schlossman expressed
J Immunol
34.
Stashenko
Proc Nail 35. horst antigen
36.
Anderson
on normal,
of cell
Acad
KC,
Marti
distinct
from
II. G,
BF,
Nadler LM, Bhan AK, Schooley RT: cell surface marker of human B cell by Epstein Barr virus. J Immunol
Lennert
of
K:
Bates
and
LM,
Hardy
after
human
Characterization BI.
J Immunol
that
and
neoplastic
disease
lymphoid
associated
tissue:
Reed-Sternberg
1979
43. Evans RL, Wall Testa CM, Good RA: Inhibition
ofcell
DW,
Platsoucas
CD, Siegal
Thymus-dependent mediated
FP, Fikrig
membrane
lympholysis
SM,
antigens
by monoclonal
in
antibod-
Acad Sci USA 78:544, 1981 G, H#{228}mmerling GJ, M#{246}ller P: Immunohistochemical study of the expression of epithelium-specific antigen Egp34 in normal and malignant tissues using monoclonal antibody HEA125. Cancer Res (in press) 45. Anderson KC, Boyd AW, Fisher DC, Leslie D, Schlossman SF, Nadler LM: Hairy cell leukemia: a tumor of pre-plasma cells. ies to the TH2 44.
antigen.
Momburg
Proc
F,
NatI
Moldenhauer
1985
1:761, 1986
Freedman Schlossman
AS, Boyd AW, Anderson KC, SF, Nadler LM: Immunologic
Fisher DC, Pinkus heterogeneity of
large
cell H,
Nadler
Immature sinus population. Am J Pathol I 17:44, 1984 50. Dc Almeida PC, Harris NL, Bhan AK: Characterization of immature sinus histiocytes (monocytoid cells) in reactive lymph nodes by use of monoclonal antibodies. Hum Pathol 15:330, 1984 5 1 . Sohn CC, Sheibani K, Winberg CD, Rappaport H: Monocytoid B lymphocytes: Their relation to the patterns of the acquired immunodeficiency syndrome (AIDS) and AIDS-related lymphadenopathy. Hum Pathol 16:979, 1985
LM,
Springer, E, Daley
antigen B lymphoSF:
Expres-
activation.
52.
R, van Agthoven 128:1941,
Hodgkin’s
Evidence cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 66:848, 1985 41 . Kamoun M, Martin Pi, Hansen JA, Brown MA, Siadak AN, Nowenski R: Identification of human T lymphocyte surface protein associated with the E-rosette receptor. i Exp Med I 53:207, 1981 42. Reinherz EL, Kung PC, Goldstein G, Schlossman SF: A monoclonal antibody with selective reactivity with functional mature human thymocytes and all peripheral human T cells. J Immunol
antigen
Stein
malignant
human
the
J, R,
49.
B lymphocyte
ofa
expression
Ki- 1 in reactive
N, Wainscoat H, Schwarting
diffuse
M, Park
R, Schlossman
The
Gerdes J, O’Connor B, Delsol G, Lemke
antibody: A non-B” lym-
York,
New
leukemia.
GS,
1983
markers
SF:
Haynes
3 (alpha Blood 65:974,
G, Schwartz
B-lymphocyte-associated
Sci USA 78:3848, 1981 LM, Stashenko P. Hardy
C, Schlossman (B2)
EL,
Typing
mitogen-activated,
131:244, P. Nadler
surface
Nadler
Reinherz
Leukocyte
SF: B4, a human
cytes. sion
in
ID (eds):
Bernstein
monoclonal of “non-T,
cell
antibod-
S-HCL
Thorley-Lawson DA, (EBVCS), an early activation, is superinduced 134:3007, 1985 40. Stein H, Mason DY, Pallesen G, Gatter K, Falini 39.
Blast-2
48.
1980 32.
of hairy
monoclonal
46. San Miguel iF, Caballero MD, Gonzales M, Zola H, Borrasca AL: Immunological phenotype of neoplasms involving the B cell in the last step of differentiation. Br i Haematol 62:75, 1986 47. Erber WN, Mynheer LC, Mason DY: APAAP labelling of blood and bone-marrow samples for phenotyping leukaemia. Lancet
antigen
J Immunol
alpha
Blood6S:620,
anti-
leukemia
The
and
RE,
J, Schlossman
lymphoblastic in vitro.
CY:
Leu-l4)
DY:
1983
acute antibody
H, Wang
1985
man:
AF, Ziegler A: Production of monoclonal group A erythrocytes, HLA and other human cell gens-New tools for genetic analysis. Cell 14:9, 1974 29. Charron Di, McDevitt HO: Characterization antigens
Am
1986
Williams
region
Caillaud
R, Stein
S-HCLI (alpha allow the diagnosis
123:1312,
1982
27.
28.
Mann prominent
of
50:277,
J Surg
work-
WP,
ofextranodal
S: Primary non-Hodgkin’s Cancer 50:2486, 1982
lymphoma
S. Bowman
cutaneous
pema
nostic
including
international
1983
Levitt
26.
cases
564
by the
I 13:207, 1983
SB,
associated
of
classified
J Pathol
A, Murphy
J,
childhood
evaluation
lymphomas
Schwarting
alpha
Leu-M5)
Kid
group.
study
38. ies
Hematol Oncol 2:269, 1984 Tubbs RR, Fishleder A, Weiss RA, Savage RA, Sebek BA, JK: lmmunohistologic cellular phenotypes of lymphoprolifer-
lymphoma
257
Kid
of
ET AL
A, Ter-
B cell-specific 1981
Moldenhauer G, D#{246}rkenB, Schwartz R, Pezzutto A, H#{228}mmerling Gi: Characterization of a human B lymphocytespecific antigen defined by monoclonal antibodies HD6 and HD39, in Reinherz EL, Haynes BF, Nadler LM, Bernstein ID (eds): Leukocyte Typing II. New York, Springer, 1986, p97 37. D#{246}rkenB, Moldenhauer G, Pezzutto A, Schwartz R, Feller A, Kiesel 5, Nadler LM: HD39 (B3), a B lineage-restricted antigen whose cell surface expression is limited to resting and activated human B lymphocytes. J Immunol 136:1, 1986
sinus
Pins
148:159, 53.
MA,
histiocytosis:
54.
Woda
65:630,
1985
Rivas
C, Morente
M, Oliva
A
monocytoid
B-lymphoid
H, Rubio
BA,
Racklin antigens
B, Rappaport
“B”
on
F, Fellous
M, Dron beta 2-microglobulin
by interferon.
H:
large
Altered
cell
i Pathol
expression
lymphomas.
Zinkernagel
Immunogenetics RM,
M, Tovey mRNA
of
Blood
M, Revel M: Presence of in Daudi cells: Induction
17:125, 1983 Doherty
PC:
MHC
cytotoxic
on the biological role of polymorphic major antigens determining T cell restriction-specificity, responsiveness. Adv Immunol 27:51, 1979 Studies
C: Immature
reaction.
1981 Rosa
an abnormal 55.
Blood
Lennert K, Mason DY, Liangru 5, Ziegler A: histiocytes. Their identification as a novel B-cell
1986
histocompatibility 57:802,
lymphoma.
T
cells:
transplantation function and
From bloodjournal.hematologylibrary.org by guest on July 10, 2011. For personal use only.
MCCL
56. and
OF B CELL
TYPE
Sanderson
AR,
1095
Beverley
immunoselection
Today4:2ll, 57.
in
the
PCL:
Interferon,
pathway
to
M,
K, Pollard
C, Cancino
Han T, Henderson E, Ozer H: Non-Hodgkin’s lymphoma Problems in the use of heterologous and monoclonal Leuk Res 7:523, 1983
ing:
Stein cal
Pallesen
G, Beverley
PCL,
of non-B,
non-T
H: Nature on
study
frozen
tissues
Lane
EB,
Madsen
monoclonal
59.
Anderson
antigens
SF,
terminal 63.
60. chemical
Bates LM:
Blood
Krajewski
and 63:1424,
AS, Guy
analysis
non-Hodgkin’s
61.
KC, Nadler
of
M, Mason
DY,
antibodies.
anti-class
II
Guy K, Krajewski
Slaughenhoupt
BL,
Immunol
J Clin
Pinkus
GS,
of human
B cell-associated
lymphomas:
A model
of human
64.
96:442,
MHC
J Pathol AS, Dewar
B-cell
excitation.
B cell
with
Clement class
complex class
Cossar II
D: Immunohistoantigens
145:185, 1985 AE: Expression
in
B-cell
class
ofhuman
Crow
1 20: 1 480,
MK,
Pernis
B lymphocytes complex
HG: the
1978 B:
Anti-
is inhibited antibodies.
by Cell
LoCascio
NJ,
Ovnic
M,
Haughton
G:
Two
II (Ia) molecules: T-cell stimulation and Proc Natl Acad Sci USA 82:516, 1985 LT, Tedder TF, Gartland GL: Antibodies reactive ofclass
human
encoded B cell
for
by the
activation.
major i
histocompatibility Immunol
136:2375,
I986
R, Martinez-Maza 0, Guy K: Monclonal antibodies HLA-DR antigens replace T helper cells in activation of B lymphocytes. Proc Natl Acad Sci USA 80:3456, 1983 66.
against of MHC
lympho-
1985
II antigens inhibit
N,
histocompatibility
RB,
functions
J Immunol
Agostino
stimulation
Corley
65.
1984 AE,
VR, major
and non-Hodgkin’s
Wang CY, Winchester R, Kunkel of human “Ia-like” antigens during
of B cell development.
immunoglobulin
Expression
K, Dewar
human
lymphomas.
MP,
J, Fu SM,
stages
leukaemia
1986
expression
Bonagura
separate
on leukemias
differentiation.
of
phenotyp-
Pathol 37:91 1, 1984 Schlossman
Patterns
antibodies.
An immunohistologi-
lymphomas:
using
M,
53:161,
Halper
62.
J, Minato
Minowada
B-cell
human
ma.
Immunol
1983
Barcos
58.
II antigens in Br J Cancer
f32-microglobulin
malignancy.
Palacios