Analysis of the role of interferon‐gamma, interleukin 2 and a third factor distinct from interferon‐gamma and interleukin 2 on human B cell proliferation. Evidence that they act at different times after B cell activation

Abstract

Recombinant interferon-gamma (rIFN-γ) was able to induce proliferation of human tonsillar B cells activated with suboptimal concentrations of anti-μ antibody. The B cell growth factor (BCGF) activity of rIFN-γ was not due to substances contaminating the IFN-γ preparation, nor was it mediated by factors released by T cells or large granular lymphocytes following activation by rIFN-γ. The response of B cells to rIFN-γ peaked on day 3 of culture and rapidly declined thereafter, whereas the response of parallel anti-μ-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-γ 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-μ-stimulated B cell cultures of very low concentrations of rIFN-γ potentiated the B cell proliferation promoted by rIL2. The simultaneous addition of monoclonal antibodies against IFN-γ and T cell activation antigen to anti-μ-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-γ, still maintained its ability to promote proliferation of anti-μ-activated B cells after complete removal of IFN-γ. Taken together, our data indicate that although some T cell clones are able to produce a BCGF distinct from both IFN-γ and IL2, these lymphokines account for most of the BCGF activity of supernatants obtained from polyclonal T cell populations. They also suggest that IFN-γ and the BCGF distinct from IFN-γ and IL 2 act primarily in the earlier phases of B cell activation and potentiate the proliferative response of activated B cells to IL2.