A Monoclonal Antibody Defining Human B Cell Differentiation Antigen (HLB-1 Antigen)

A new monoclonal antibody specific for human B cell differentiation antigen (HLB-1) is produced by a hybridoma established by fusion of splenocytes of mice immunized with the Epstein-Barr virus (EBV)-transformed peripheral B cell line, RPMI-8057. This monoclonal, antibody designated anti-HLB-1 monoclonal antibody (anti-HLB-1), reacted with surface immunoglobulin (sIg)-positive B cells of normal peripheral blood and lymphoid tissues and sIg-positive leukemic cells. The cells of T cell leukemia, non-T non-B acute lymphoblastic leukemia (ALL) and nonlymphoid leukemia were HLB-1 negative. These data were further confirmed by studying a panel of cultured human hematopoietic cell lines. Anti-HLB-1 reacted with B cell lines derived from pre-B, Burkitt's lymphoma, B cell type ALL and EBV-transformed peripheral B cells. Anti-HLB-1 was reactive with only one of three human myeloma cell lines, and with none of the T cell, myeloid and non-T non-B ALL cell lines. This newly defined HLB-1 antigen is different from other conventional human B cell markers such as sIg, Ia antigens, and receptors for the Fc portion of Ig and complement C3.     

Functional analysis of human T cell subsets defined by monoclonal antibodies. V. Suppressor cells within the activated OKT4+ population belong to a distinct subset

In the present report, we characterize a monoclonal antibody directed at a surface differentiation antigen on human T cells. The monoclonal antibody, OKT17, recognizes a cell surface antigen present on the majority of resting normal peripheral T cells. In contrast, OKT17 is unreactive with normal B cells, B cell lines, T cell lines, or SIg+ CLL. Interestingly, after activation, the antigen recognized by OKT17 is lost from a subset of OKT4+ cells. We took advantage of this finding to explore further the functional heterogeneity within activated OKT4+ cells. Evidence was obtained that the PWM-activated OKT4+ subset remaining after depletion of OKT17-reactive T cells (OKT4+ 17-) contains radiosensitive helperr cells but is devoid of suppressor cells. In contrast, the activated OKT4+ 17+ population contains potent radiosensitive suppressor cells as well as radioresistant helpe cells. Taken together, these studies suggest that the OKT17 monoclonal antibody can differentiate two functionally mature, activated OKT4+ human T cells: OKT4+ OKT17+ radiosensitive suppressor cells and OKT4+ 17- radiosensitive helper cells.     

In vitro maturation of B cells in chronic lymphocytic leukemia. I. Synergistic action of phorbol ester and interleukin 2 in the induction of Tac antigen expression and interleukin 2 responsiveness in leukemic B cells

Recent evidence indicates that interleukin 2 (IL 2), formerly thought to serve as growth factor exclusively for activated T cells, is directly involved in human B cell differentiation. We have investigated the role of IL 2 and IL 2 receptors (as defined by monoclonal anti-Tac antibody) in the phorbol ester-induced in vitro maturation of leukemic B cells from patients with chronic lymphocytic leukemia (CLL). Peripheral blood lymphocytes from B cells from CLL patients with high (greater than 10(5)/microliters) white blood cell counts were depleted of residual T lymphocytes and low-density cells (primarily macrophages) by consecutive steps of E rosetting, complement-mediated lysis of OKT3+ and OKT4+ cells, and Percoll density gradient centrifugation. No OKT3+ T cells were detectable in these cell populations before or after culture. When incubated for 3 days with phorbol ester plus recombinant human IL 2 (rIL 2), 12 to 57% of highly purified B cells from four of five tested patients expressed Tac antigen. Both phorbol ester and rIL 2 were required for maximal Tac antigen expression. Functional studies revealed that phorbol ester-activated (but not resting) CLL B cells responded to rIL 2 with [3H]thymidine incorporation and with enhanced secretion of IgM. Tac+ B cells were isolated in two cases on a fluorescence-activated cell sorter. In one patient, stimulation of Tac+ B cells with rIL 2 resulted in enhanced [3H]thymidine incorporation but no change in IgM secretion, as compared with Tac- B cells; in the second patient, stimulation of Tac+ B cells with rIL 2 did not result in [3H]thymidine uptake, but did result in significant IgM secretion. These findings indicate that certain leukemic B lymphocytes can be induced to express IL 2 receptors and respond to IL 2. The use of resting clonal B cell populations arrested at distinct stages of differentiation may help to better define the stage(s) at which IL 2 acts directly on B cells to induce proliferation and/or terminal differentiation.     

CXCL12 is a costimulator for CD4+ T cell activation and proliferation in chronic lymphocytic leukemia patients

Activated T cells from patients with chronic lymphocytic leukemia (CLL) provide survival and proliferative signals to the leukemic clone within lymphoid tissues. Recruitment of both, CLL cells and T lymphocytes, to this supportive microenvironment greatly depends on CXCL12 production by stromal and myeloid cells. CXCL12 also supplies survival stimuli to leukemic B cells, but whether it exerts stimulatory effects on T lymphocytes from CLL patients is unknown. In order to evaluate the capacity of CXCL12 to increase CD4⁺ T cell activation and proliferation in CLL patients, peripheral blood mononuclear cells were cultured with or without recombinant human CXCL12 or autologous nurse-like cells, and then T cell activation was induced by anti-CD3 mAb. CXCL12 increases the proliferation and the expression of CD25, CD69, CD154, and IFNγ on CD3-stimulated CD4⁺ T cells from CLL patients, similarly in T cells from ZAP-70⁺ to ZAP-70^? patients. Autologous nurse-like cells establish a close contact with CD4⁺ T cells and increase their activation and proliferation partially through a CXCR4-dependent mechanism. In addition, we found that activated T cells in the presence of CXCL12 enhance the activation and proliferation of the leukemic clone. In conclusion, CXCL12 production by lymphoid tissue microenvironment in CLL patients might play a key dual role on T cell physiology, functioning not only as a chemoattractant but also as a costimulatory factor for activated T cells.     

In vitro engagement of CD3 and CD28 corrects T cell defects in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of leukemic B cells concomitant with immunological abnormalities and depressed immune responses. The T cell abnormalities found in CLL patients are thought to increase the risk of infection and hamper immune recognition and elimination of leukemic cells. We evaluated whether providing signals through CD3 and CD28 would correct some of these T cell defects. PBMC were incubated with anti-CD3 and anti-CD28 mAbs conjugated to superparamagnetic beads for 12-14 days. This resulted in a 1400-fold increase in T cell numbers. Activated T cells expressed high levels of CD25, CD54, CD137, and CD154, and produced IFN-gamma, TNF-alpha, and GM-CSF. The mean T cell composition of cultures increased from approximately 6% to >90% and leukemic B cells decreased from a mean of approximately 85% to 0.1% or less. Leukemic B cells up-regulated expression of CD54, CD80, CD86, and CD95. Receptor up-regulation required direct cell contact with the activated T cells and could be blocked with anti-CD154 mAb, suggesting that the CD40-CD40L pathway helped mediate these effects. Poor T cell responses to allostimulation were corrected by the activation and expansion process. The skewing in the TCR repertoire returned to normal, or near normal following the culture process in eight of nine patients with abnormal TCR repertoires. Activated T cells had potent in vitro antileukemic effects in contrast to nonactivated T cells. Based upon these findings, a clinical trial has been initiated to test the potential therapeutic effects of T cells activated using this approach in patients with CLL.     

A novel cell surface antigen (T305) found in increased frequency on acute leukemia cells and in autoimmune disease states

Monoclonal antibody T305, prepared by immunizing mice with the T-ALL derived cell line RPMI-8402, immunoprecipitates a single chain glycoprotein with m.w. 160,000 daltons (under reducing conditions) or 180,000 daltons (under nonreducing conditions). In immunofluorescence assays, antibody T305 reacted with a subpopulation of T cells in normal blood (22 +/- 6%), thymus (28 +/- 11%), and lymph node (24 +/- 6%). Increased frequency of T cells reactive with antibody T305 was found in peripheral blood of patients with infectious mononucleosis (greater than 80%), graft-vs-host disease after bone marrow transplantation (65 +/- 11%), acquired immunodeficiency syndrome (53 +/- 12%). The T cells in synovial fluid of patients with rheumatoid arthritis had increased frequency of antibody T305 reactive cells (59 +/- 8%) as compared to their peripheral blood (18 +/- 7%). Two color immunofluorescent studies demonstrated that the T305+ T cells predominantly co-stained with antibody Leu 2a (suppressor/cytotoxic subset) in both normals and disease state blood. After cell sorting to obtain T305+ and T305- subpopulations, we demonstrated that a) natural killer and antibody-dependent cellular cytotoxicity activity in normal blood was in the T305+ but not T305- T cells; b) cytotoxic T cells induced by mixed lymphocyte reaction were predominantly T305+; c) T305- T cells could be induced in vitro to express T305 antigen by mitogens or allogeneic B cells; d) the DNA content of T305+ and T305- T cells in normal blood was similar (greater 95% of cells with G0/G1 level); e) after mitogen stimulation, T305 antigen induction on previously T305- cells occurs before S-phase; and f) significantly more [3H]-thymidine after mitogen stimulation was incorporated by originally T305- cells than by originally T305+ cells (p less than 0.001). The T305 antigen was not restricted to T cells because it was also found on myeloid precursors in bone marrow but was not present on polymorphonuclear leukocytes, red blood cells, platelets, muscle, liver, skin, kidney, lung, or brain. Antibody T305 was found on 24/25 cases of acute leukemia (6 T-ALL, 10/11 cALL, 7 AML, and 1 AMOL) but not on 18 cases of chronic leukemia (B-CLL, T-CLL, null CLL, CML). The importance of the T305 antigen is that it is present on a high number of T cells in certain autoimmune diseases and on virtually all acute leukemia cells. Its distribution on immature and in vitro activated cells suggests that it may represent a receptor for signals related to cellular replication or differentiation.     

Identification of human peripheral T cell antigens.

A new type of differentiation antigens on human T cells was demonstrated by using a heterologous anti-human T cell serum (ATS). This type of antigen, referred to as human peripheral T cell antigen (HPTA), was found on peripheral T cells and medullary thymocytes, but not on cortical thymocytes and B cells. The percentage of ATS-reactive lymphocytes in human peripheral lymphoid organs was correlated with that of cells rosetting with sheep erythrocytes, but contrasted with the number of B cells defined by the presence of a complement (C) receptor or by rabbit anti-human B cell serum (ABS). ATS also reacted with T cells purified by nylon fiber column filtration but ABS did not. Chronic lymphocytic leukemia cells rosetted with either sheep erythrocytes or erythrocyte-antibody-complement complexes were lysed by ATS and ABS, respectively. Mitogenic responses of blood lymphocytes to phytohemagglutinin (PHA) and concanavalin-A (Con A) were abrogated by treating them with ATS and C, whereas ABS suppressed only their response to Con A. Although numerous thymus cells rosetted with SRBC, only 14% were reactive with ATS. Quantitative absorption studies demonstrated that HPTA content of the thymus cells was much lower than that of lymph node cells. Anatomical localization of ATS-reactive lymphocytes in human lymphoid organs studied by immunofluorescence indicated that they were present in the thymus-dependent paracortical areas of lymph node and in the medullary region of thymus. ABS, on the other hand, did not stain thymocytes but reacted selectively with the cells located in the lymphoid follicles of lymph node. These data, together with that from cell suspension studies, confirmed that HPTA were shared between medullary thymocytes and peripheral T cells.     

Cadmium-induced synthesis of metallothioneins in human T and B cell purified by a fluorescence activated cell sorter

Human peripheral blood lymphocytes were reacted with fluorescein-conjugated antibodies specific to T or B cell surface antigen and fractionated with a fluorescence activated cell sorter. The isolated T and B cells were examined for their capacity to synthesize metallothioneins (MTs). Analysis by gel electrophoresis indicated that both T and B cells were able to produce MTs in a Cd2+-inducible manner, suggesting that both cells types have a mechanism of protection against Cd2+ toxicity.     

A new human T-cell differentiation antigen: Unexpected expression on chronic lymphocytic leukemia cells

Monoclonal antibody 10.2 reacts with a monomorphic antigen expressed on the surface of virtually all thymocytes, as well as thymus-dependent lymphocytes in the peripheral blood and bone marrow. In contrast, antibody 10.2 did not react with normal peripheral blood B cells, monocytes, or the non-T-cell fraction of bone marrow. This complement fixing IgG2a antibody also reacted with extablished leukemic T-cell lines, but not with cell lines of either normal or malignant B-cell origin. Similarly, when tested against acute leukemia blasts, the 10.2 antibody reacted with those from patients with T-cell acute leukemia, but not with those from patients with acute null cell or non-lymphocytic leukemia. An unexpected exception to this pattern was the reaction of 10.2 antibody with leukemic cells from patients with B-cell type chronic lymphocytic leukemia. Immune precipitates formed with 10.2 antibody and detergent lysates of radiolabeled T-cells contained three polypeptides with molecular weights of 65 000, 55 000, and 50000 daltons. It has not been determined whether all three of these polypeptides contain the 10.2 antigenic determinant, or whether these proteins represent a multimeric antigen complex.PJM is a Junior Faculty Clinical Fellow of the American Cancer Society.     

A new human T-cell differentiation antigen: unexpected expression on chronic lymphocytic leukemia cells

Monoclonal antibody 10.2 reacts with a monomorphic antigen expressed on the surface of virtually all thymocytes, as well as thymus-dependent lymphocytes in the peripheral blood and bone marrow. In contrast, antibody 10.2 did not react with normal peripheral blood B cells, monocytes, or the non-T-cell fraction of bone marrow. This complement fixing IgG2a antibody also reacted with established leukemic T-cell lines, but not with cell lines of either normal or malignant B-cell origin. Similarly, when tested against acute leukemia blasts, the 10.2 antibody reacted with those from patients with T-cell acute leukemia, but not with those from patients with acute null cell or non-lymphocytic leukemia. An unexpected exception to this pattern was the reaction of 10.2 antibody with leukemic cells from patients with B-cell type chronic lymphocytic leukemia. Immune precipitates formed with 10.2 antibody and detergent lysates of radiolabeled T-cells contained three polypeptides with molecular weights of 65 000, 55 000, and 50 000 daltons. It has not been determined whether all three of these polypeptides contain the 10.2 antigenic determinant, or whether these proteins represent a multimeric antigen complex.     

Monoclonal antibody to a structure expressed on a subpopulation of rat CD8 T cell subsets.

We have developed a monoclonal antibody, RTS-1, which can divide a rat CD8 (+) peripheral T cell population into two functionally distinct subsets. The cell-surface structure defined by this antibody is a glycoprotein with a molecular weight of 220 kDa found to be a high molecular isoform of rat CD45 antigen. CD4 (+) T cells were not stained by RTS-1 antibody. The cytotoxic T cell-enriched population did not express RTS-1 epitope on the cell surface. CD8 (+) spleen cells as well as RTS-1(+)CD8(+)T cells exhibited strong inhibition on mitogen-induced immunoglobulin G production by rat B cells. Furthermore, RTS-1 antibody, but not the control antibody, abolished CD8(+)T cell-mediated inhibition of immunoglobulin G production by rat B cells. These data suggest that RTS-1 antibody recognizes a unique determinant of rat CD45 antigen that is expressed on a fraction of CD8(+) cells.     

Phenotypic modulation of chronic lymphocytic, prolymphocytic, and lymphoplasmacytic leukemia cells by TPA: induction of TRAP isoenzyme 5 and HD6 (CD22) antigen and enhancement of IgM messenger RNA

B-cell neoplasias such as CLL can be viewed as models of monoclonal populations restricted within discrete ranges of B-cell maturation. It is unknown whether other B-cell leukemias such as prolymphocytic leukemia (PLL), lymphoplasmacytoid immunocytoma (IC), and hairy cell leukemia (HCL) involve different B lineages or are malignant variants of B cells in successive stages of development along the same lineage. Therefore in vitro maturation was induced with the phorbol ester TPA in leukemic cell samples from 10 CLL, 4 PLL, and 4 IC patients. Morphologically, both plasmacytic and hairy cell-like phenomena were induced. The latter unexpected finding was confirmed by reaction with HD6 (CD22) antibody which stains HCL but is unreactive with plasma cells, multiple myeloma, and CLL cells. Tartrate-resistant acid phosphatase was demonstrated in TPA-cultured CLL, PLL, and IC cells, and the same isoenzyme band as in HCL was revealed by isoelectrofocusing. On the other hand, an increase of IgM messenger RNA was detected in up to 20% of the cells in CLL cultures by single-cell in situ hybridization with fluoro-chrome-labeled DNA probes. An abundance of IgM messenger RNA characterizes lymphoplasmacytoid cells as found in IC. Our data demonstrate that CLL, PLL, and IC can be induced to realize a common genetic program which bears characteristics of HCL indicating that these four entities are more closely related than previously thought.     

Characterization of a human B lymphocyte-specific antigen

A human B lymphocyte-specific antigen (B1) was identified and characterized by the use of a monoclonal antibody. By indirect immunofluorescence, cytotoxicity, and quantitative absorption, B1 was present on approximately 9% of the peripheral blood mononuclear cell fraction and >95% of B cells from blood and lymphoid organs in all individuals tested. Monocytes, resting and activated T cells, null cells, and tumors of T cell and myeloid origin were B1 negative. B1 was distinct from standard B cell phenotypic markers, including Ig and Ia antigen. Removal of the B1 positive population in peripheral blood eliminated all B cells capable or responding to pokeweed mitogen by maturation to Ig-producing cells.     

Circulating monoclonal IgM proteins in B cell chronic lymphocytic leukemia: their identification, characterization and relationship to membrane IgM

Accumulated evidence indicates that there is a circulating monoclonal Ig protein related to the leukemic cell-associated Ig in the majority of patients with B cell chronic lymphocytic leukemia (CLL) despite the failure to demonstrate such a protein by conventional serum electrophoresis. Methodology has been developed to reveal these hidden monoclonal bands and to show that they are related to the leukemia-associated membrane Ig (mIg). Of nine CLL cases with stainable mIgM and without discernable plasma Ig bands, marked hypogammaglobulinemia was evident in six. In the other three, a significant amount of protein was present in the gamma region. IgM was isolated from the plasma of these patients by affinity chromatography with Sepharose-4B, conjugated with affinity purified anti-human IgM antibodies. One to 3 mg were isolated from 20 to 40 ml of plasma. Agarose electrophoresis revealed a monoclonal Ig band in the isolated IgM in all cases. Eight of these IgM proteins were analyzed by high-pressure liquid chromatography. Five were found to be pentameric IgM. In the remaining three, various amounts of monomeric IgM were detected. Attempts to make anti-idiotypic antibodies to the isolated proteins have been successful. Thus far, a rabbit anti-idiotypic antiserum was obtained in one case and two mouse monoclonal anti-idiotypic antibodies in two additional cases. Immunofluorescence analysis revealed that plasma IgM and mIgM shared similar idiotypic determinants. One other monoclonal antibody was shown to be specific for a V region marker of a minor Ig population. These findings indicate that B leukemic lymphocytes do secrete a small amount of IgM and lend further support to the thesis that the maturation defect in CLL is incomplete. It is also feasible to isolate the secreted IgM and to produce anti-idiotypic antibodies to them. In view of the potential therapeutic effect of anti-idiotypic antibodies, this may offer an alternative and efficient approach to generate a large panel of anti-idiotypic antibodies for clinical trials. The possibility also exists that this approach is applicable to other B cell proliferative disorders such as the non-Hodgkin B cell lymphomas.     

A monoclonal antibody detecting a 39,000 m.w. molecule that is present on B lymphocytes and chronic lymphocytic leukemia cells but is rare on acute lymphocytic leukemia blasts

Monoclonal antibody 41H.16 was produced by using the hybridoma methodology in the mouse system with cells from a patient with hairy cell leukemia as the immunogen. This antibody reacts with the majority of Slg+ cells in the peripheral blood and with all B lymphoblastoid cell lines. Reactivity with conventional Ig determinants, Fc or C3 receptors, has been excluded. The antibody reacted with cells from 68 patients with CLL but showed no reactivity with cells in 69 specimens from patients with non-T, non-B ALL. The apparent m.w. of the antigen detected by this antibody is approximately 39,000.     

Development and distribution of a human B cell subpopulation identified by the HB-4 monoclonal antibody

Monoclonal antibodies have been successfully used to identify B cell differentiation antigens, few of which mark discrete B cell subpopulations. We have produced a monoclonal antibody, HB-4, against a cell surface antigen on the human B cell line, BJAB, which has an unusual distribution on normal lymphoid cells. HB-4, an IgM antibody, was found to react with an antigen that is expressed by a subpopulation of B cells, approximately 50% of natural killer cells, and not by other types of cells in bone marrow, blood, and lymphoid tissues. In two-color immunofluorescence assays, the HB-4-reactive antigen was found on less than 5% of immature IgM+ B cells in fetal liver and bone marrow and on 25% of B cells in fetal spleen. The HB-4 antibody reacted with 40% of IgM+ cells in newborn blood and 60% of B cells in adult blood. In contrast, only 2 to 26% of IgM+ B cells in the peripheral lymphoid tissues of adults were HB-4+. HB-4+ B cells could be induced to proliferate by cross-linkage of their surface immunoglobulins but not by T cell-derived growth factors. The subpopulation of activated B cells that is responsive to T cell-derived differentiation factors was HB-4-, as were plasma cells. The HB-4 antibody was reactive with some but not all B cell malignancies and cell lines, and not with malignancies or cell lines of other lineages. The HB-4 antigen may therefore serve as a useful nonimmunoglobulin marker for the identification of a subpopulation of mature resting B cells that are present in the highest frequency in the circulation.     

Monoclonal antibodies identifying a novel T-Cell antigen and Ia antigens of human lymphocytes

We describe here two new monoclonal antibodies that react with surface antigens of human lymphocytes. Antibody 7.2 identified a determinant on the framework region of the human Ia antigen. It was cytotoxic for all cultured B-cell lines, normal B cells, and monocytes. The antibody was not cytotoxic for normal T cells or for established T leukemic cell lines. In immune precipitation assays, the 7.2 antibody reacted with a bimolecular complex of two chains that resolved in polyacrylamide gels as polypeptides with molecular weights of 29000 and 34000 daltons. These precipitation results were analogous to those achieved with a rabbit antiserum prepared against human Ia antigens. Antibody 9.3 identified a determinant on the framework region of a T-cell antigen. It was cytotoxic for 50–80% of peripheral T cells and for 20–50% of thymocytes. It was not cytotoxic for cultured B-cell lines, normal B cells, or monocytes. In immune precipitation assays, the 9.3 antibody reacted with a single polypeptide with a molecular weight of 44000 daltons. Due to the expression of this antigen on a limited subpopulation of human T cells, we have designated the antigen HuLyt-1.     

Characterization of a monoclonal antibody to guinea pig T cells that inhibits rosette formation of the cells with rabbit erythrocytes: similarity of the antigen to E-receptor on human T cells

A monoclonal antibody, GPT-1, was prepared by fusion of the splenic cells of mice immunized with guinea pig thymocytes with a mouse myeloma cell line. GPT-1 completely inhibited spontaneous rosette formation of T cells with papain-treated rabbit erythrocytes. GPT-1 reacted with 90% of thymocytes, 70% of peripheral blood lymphocytes, and 45% of splenic lymphocytes, but not with B cells. These results indicate that GPT-1 has pan-T reactivity. The antibody specifically bound to a single polypeptide chain with a molecular size of 50-65 kD. The surface density of the antigen was higher on thymocytes than on peripheral T cells, suggesting that the antigen is a certain differentiation antigen on T cells. Phytohemagglutinin-activated T cells expressed more antigen molecules than resting T cells. In addition, GPT-1 suppressed the proliferation of T cells induced by the mitogen, indicating that GPT-1 recognizes a T cell-specific surface antigen which is associated with T cell activation. Based on these results, it was concluded that GPT-1 reacts with a guinea pig T cell surface antigen which is similar to the E-receptor protein on human T cells (CD2 molecule).     

The isolation and characterization of the human suppressor inducer T cell subset

Immunization of mice with lower primate lymphoid cells has provided a useful strategy for raising monoclonal antibodies against functionally important surface determinants on human T lymphocytes. We have developed a monoclonal antibody, anti-2H4, which defines functionally unique human T cell subsets. This anti-2H4 antibody was reactive with approximately 42% of unfractionated T cells, 41% of T4+ inducer cells, and was reactive with approximately 54% of T8+ cytotoxic/suppressor population. Anti-2H4 was not reactive with human thymocytes, but reacted with subsets of peripheral blood B cells and null cells. This antibody subdivided peripheral blood T4+ cells into two functionally distinct populations. The T4+2H4+ subset proliferate well to concanavalin A (Con A) stimulation, but poorly to soluble antigen stimulation, and provides poor help to B cells for PWM-induced Ig synthesis. The T4+2H4- subset, in contrast, proliferates poorly upon stimulation with Con A, but well on exposure to soluble antigen, and provides a good helper signal for PWM-induced Ig synthesis. What is, perhaps, most important, the T4+2H4+ subset functions as the inducer of the T8+ suppressor cells. Previous attempts to define the latter subset of cells has relied heavily on the use of specific autoantibodies present in the sera of patients with juvenile rheumatoid arthritis (JRA) and systemic lupus erythematosus (SLE). The present results suggest that anti-2H4 antibody defines the human suppressor induced subset of lymphocyte previously described as T4+JRA+. Last, the results reemphasize the previously documented remarkable structural conservation of certain T cell-specific determinants on lymphocytes of phylogenetically distant primates.     

Interleukin 2 acts directly on a Tac-positive cloned B cell line established from a patient with adult T cell leukemia

A Tac-positive B cell line termed K3B was established from a patient with adult T cell leukemia (ATL). This cell line had EBNA antigen and human T cell leukemic virus (HTLV) provirus besides B1 antigen and surface immunoglobulin. A cloned Tac-positive B cell line termed K3B01 was obtained from K3B by the limiting dilution method. The K3B01 cells were shown to absorb IL 2 activity in a tonsillar IL 2 preparation. By using this cloned cell line and a purified recombinant IL 2 preparation, it was shown that the proliferation of K3B01 cells was enhanced by the addition of recombinant IL 2. Moreover, this response was inhibited by anti-Tac antibody. These results demonstrate definitively that IL 2 acts directly on B cells through IL 2 receptors on them.