Modulation of IL-2-induced human B cell proliferation in the presence of human 50-kDa B cell growth factor and IL-4.
Several human T cell derived factors capable of stimulating human B cells to synthesize DNA have been previously described. One such factor exhibits an apparent m.w. of 50,000 Da and has been termed 50-kDa-B cell growth factor (BCGF). In this report, we show that a human B cell proliferation pathway based on the sequential action of anti-mu antibody, 50-kDa-BCGF and IL-2 is inhibited in the presence of human rIL-4. Although IL-4 itself is capable of triggering B cell DNA synthesis as measured at 72 h, this lymphokine inhibits, in a dose-related manner, the 50-kDa-BCGF driven response of B cells to IL-2 when such proliferation is determined after 144 h. This inhibition takes place at an early step of the B cell activation and does not require the presence of IL-4 during the whole culture period. Such inhibitory activity of IL-4 is specific to the IL-2-induced B cell proliferation because DNA synthesis measured in the presence of semi-purified human 12-kDa-BCGF is not affected by the presence of IL-4. Our results suggest that a particular pathway of human B cell activation leading to the proliferation of these cells in the presence of IL-2 could be either up- or down-modulated by 50-kDa-BCGF and IL-4, respectively.
Vazquez
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Roger Williams General Hospital, Department of Pathology, Providence, RI 02908.
Mills
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Maizel
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D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2; D015847:Interleukin-4; D007378:Interleukins / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008970:Molecular Weight; D011994:Recombinant Proteins / Q000494:pharmacology; D013205:Staphylococcal Protein A; D013997:Time Factors
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D013205:Staphylococcal Protein A; D015847:Interleukin-4