Analysis of the role of interferon-gamma, interleukin 2 and a third factor distinct from interferon-gamma and interleukin 2 in human B cell proliferation. Evidence that they act at different times after B cell activation.
Recombinant interferon-gamma (rIFN-gamma) was able to induce proliferation of human tonsillar B cells activated with suboptimal concentrations of anti-mu antibody. The B cell growth factor (BCGF) activity of rIFN-gamma was not due to substances contaminating the IFN-gamma preparation, nor was it mediated by factors released by T cells or large granular lymphocytes following activation by rIFN-gamma. The response of B cells to rIFN-gamma peaked on day 3 of culture and rapidly declined thereafter, whereas the response of parallel anti-mu-activated B cell cultures to recombinant interleukin 2 (rIL2) appeared on day 3, but continued at least until day 5. In addition, B cells responsive to rIFN-gamma could be at least in part separated from those responsive to rIL2, the former being primarily contained in B cell fractions enriched for high-density small B lymphocytes. Finally, the addition to anti-mu-stimulated B cell cultures of very low concentrations of rIFN-gamma potentiated the B cell proliferation promoted by rIL2. The simultaneous addition of monoclonal antibodies against IFN-gamma and T cell activation antigen to anti-mu-stimulated B cell cultures strongly reduced the B cell proliferative response promoted by three different crude BCGF preparations obtained by polyclonal T cell activation in mixed lymphocyte culture. However, the supernatant from a T cell clone (DP5/11) apparently free of IL2, which manifested a BCGF activity similar to that of rIFN-gamma, still maintained its ability to promote proliferation of anti-mu-activated B cells after complete removal of IFN-gamma. Taken together, our data indicate that although some T cell clones are able to produce a BCGF distinct from both IFN-gamma and IL2, these lymphokines account for most of the BCGF activity of supernatants obtained from polyclonal T cell populations. They also suggest that IFN-gamma and the BCGF distinct from IFN-gamma and IL2 act primarily in the earlier phases of B cell activation and potentiate the proliferative response of activated B cells to IL2.
D000276:Adjuvants, Immunologic / Q000502:physiology; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D002469:Cell Separation; D002474:Cell-Free System; D002999:Clone Cells / Q000276:immunology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D011994:Recombinant Proteins / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D006133:Growth Substances; D007075:Immunoglobulin M; D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins; C044203:anti-IgM; D015847:Interleukin-4; D007371:Interferon-gamma