Antiproliferative effect of antilymphocyte globulins on B cells and B-cell lines.
Antithymocyte and antilymphocyte globulins (ALG) are currently used as immunosuppressive agents in organ transplantation and for the treatment of acute graft-versus-host disease and aplastic anemia. Since any type of immunosuppressive treatment is known to carry the risk of developing B-cell lymphoproliferative disorders, we investigated the in vitro effect of ALG on human B-cell activation and proliferation. The data demonstrate that whatever the source of lymphocytes used for ALG preparation (thymocytes, thoracic duct lymphocytes, B- or T-cell lines), (1) ALG react with both B- and T-cell lines, and (2) ALG contain antibodies specific for B cells (eg, CD21) or common to T and B cells (eg anti-beta 2-microglobulin, anti-HLA-DR, CD18, CD11a) in addition to T-cell-specific antibodies. Unlike all other T-cell mitogens tested (Concanavalin A [Con A], Pokeweek mitogen [PWM], CD3 and CD2 antibodies), ALG do not trigger B-cell differentiation into immunoglobulin-secreting cells at concentrations which induce maximum T-cell proliferation. This effect could be attributed to a direct interaction of ALG with B lymphocytes as shown by the capacity of ALG to block the response of purified B cells to a variety of activators. Furthermore, all the ALG tested were shown to inhibit the proliferation of six of the seven Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and six of the seven Burkitt's lymphoma cell lines studied. This selective B-cell antiproliferative property of ALG was not reproduced with CD11a, CD18, CD21, CD24, or anti-HLA-DR monoclonal antibodies (MoAbs). These results suggest that, although suppressing T-cell responses, ALG treatment may directly control B cell proliferation to some extent, in keeping with the relatively low risk of posttransplant lymphoproliferative disorders reported with ALG.
Bonnefoy-Berard
N
N
INSERM U80 CNRS URA, Hôpital E. Herriot, Lyon, France.
Flacher
M
M
Revillard
J P
JP
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008934:Mitogens; D014066:Palatine Tonsil / Q000276:immunology
D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D008934:Mitogens