Activation of human B cells: alternate options for initial triggering and effects of nonmitogenic concentrations of anti-IgM antibodies on resting and activated cells.
The monoclonal antibody 1F5, which is reactive with the CD20 (Bp 35) pan-B cell antigen, was shown to activate resting human peripheral blood B cells into the middle to late G1 phase of the cell cycle. However, in contrast to F(ab')2 fragments of polyclonal anti-mu, 1F5 synergized only weakly with B cell growth factor (BCGF) for DNA synthesis in these cells. We provide evidence that the CD20 molecule and surface immunoglobulin represent two alternative activation pathways in resting B cells. We also show that anti-immunoglobulins, during co-stimulation with BCGF, may play an important role in G1 as well as for the initial cell triggering. Thus, anti-mu in nonmitogenic concentrations was shown to provoke distinct effects on 1F5-pretreated G1 cells, as monitored by increases in cellular volumes as well as in cytoplasmic Ca2+ levels. Moreover, anti-mu could increase c-myc mRNA levels in 1F5-primed cells, implying that c-myc expression can be regulated in G1 as well as during the initial G0 to G1 transition. Partially purified human BCGF neither induced G1 entry in resting peripheral blood cells nor primed the cells for DNA synthesis. The finding that BCGF did not influence c-myc mRNA levels in resting or in activated B cells suggests that its mitogenic action does not involve the c-myc function.
D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology*; D015847:Interleukin-4; D007399:Interphase; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000096:biosynthesis
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D006133:Growth Substances; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C044203:anti-IgM; D015847:Interleukin-4; D002118:Calcium