IL-4 (B cell stimulatory factor 1) overcomes Fc gamma receptor-mediated inhibition of mouse B lymphocyte proliferation without affecting inhibition of c-myc mRNA induction.
Mouse B cells are stimulated to proliferate by Fab'2 fragments of rabbit anti-mouse Ig antibodies. Proliferation is inhibited, however, in the presence of IgG anti-mouse Ig. We have previously shown that this inhibition is mediated by binding of the IgG anti-Ig to receptors for Fc gamma R on B cells. This report describes conditions under which IgG anti-mu or anti-delta will induce proliferation despite Fc gamma R engagement. Culture supernatants of Con A-stimulated, Il-4-secreting Th cell lines, but not of Il-2-secreting Th cell lines, will co-stimulate with IgG anti-Ig to induce small B cells to incorporate [3H]TdR. This co-mitogenic activity is inhibitable by anti-IL-4 antibodies and can also be induced by Il-4 affinity purified from the T cell supernatants or by supernatants containing rIl-4. B cells precultured with Il-4 for 18 h, while still expressing normal levels of Fc gamma R, also proliferate to IgG anti-Ig. We have previously shown that Fc gamma R-mIg cross-linking will inhibit mIg-dependent increases in c-myc mRNA levels. We investigated whether Il-4 allows B cells to respond to IgG anti-Ig by elevating c-myc. The data show that Il-4 has little effect on c-myc mRNA levels in either IgG or Fab'2 anti-Ig-containing cultures.
Phillips
N E
NE
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 10609.
Gravel
K A
KA
Tumas
K
K
Parker
D C
DC
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D002474:Cell-Free System; D003208:Concanavalin A; D003432:Cross-Linking Reagents; D005260:Female; D007074:Immunoglobulin G / Q000502:physiology; D007075:Immunoglobulin M / Q000276:immunology; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger / Q000096:biosynthesis*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011961:Receptors, Fc / Q000502:physiology*; D017452:Receptors, IgG; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007378:Interleukins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; C044203:anti-IgM; D003208:Concanavalin A; D015847:Interleukin-4