Analysis of cell proliferation and mu-RNA processing during activation of mouse B-cells by anti-mu and T lymphokines.
Anti-immunoglobulin (anti-Ig, anti-mu is commonly used) activates resting mouse B-cells to proliferate but not to differentiate and secrete Ig. Differentiation requires additional help from T-cells including soluble factors such as lymphokines. The capability of lymphokines, alone and in combination, to promote the differentiation of anti-mu activated B-cells has been investigated. Some lymphokines, like interleukin (IL) 2 and 3, as well as human-interferon beta-2 (IL-6), have no significant effect on differentiation. IL-4 and 5 maintain cell growth but do not lead to differentiation, which requires multiple factors present in ConA supernatant or partially purified TRF. Anti-mu and interferon-gamma (IFN-gamma) exert both positive and negative effects on B-cell maturation. Anti-mu induces cell proliferation. IFN-gamma enhances Ig transcription, but it has no apparent proliferation or differentiation activity. Anti-mu and IFN-gamma inhibit Ig secretion by causing the accumulation of nuclear mu-RNA precursors. Although phorbol ester plus ionomycin induce cell proliferation, the negative effect of anti-mu in RNA processing could not be mimicked by these reagents. I show that anti-mu and IFN-gamma interfere with the splicing of nuclear hnRNA. This phenomenon is independent of known 2'-5'(A)n synthetase activity. The data suggest that post-transcriptional regulation of mu-RNA processing might be a critical event in controlling the generation of the plasma cells (which secrete IgM), memory precursor cells or abortive cells (both of which do not secrete IgM).
Chen
U
U
Basel Institute for Immunology, Switzerland.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D005786:Gene Expression Regulation / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000502:physiology*; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010703:Phorbol Esters / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology; D014158:Transcription, Genetic
D000888:Antibodies, Anti-Idiotypic; D007148:Immunoglobulin mu-Chains; D008222:Lymphokines; D010703:Phorbol Esters; D012333:RNA, Messenger; D015759:Ionomycin; D007371:Interferon-gamma