Synergy of B cell growth factor and interleukin 2 in the proliferation of activated human B cells

Abstract

The activity of purified interleukin 2 (IL2), obtained by the recombinant DNA technology, on the proliferative response of human B cells stimulated with low concentrations of anti-mu antibody was investigated. Recombinant IL2 was capable of augmenting the proliferative response of anti-mu-activated B cells and the T cell activation (Tac) antigen was expressed on a substantial proportion of normal B cells stimulated with anti-mu antibody. However, crude supernatants from protein A-stimulated peripheral blood mononuclear cells, which were found to possess both IL2 and B cell growth factor (BCGF) activities, maintained the ability to promote proliferation of anti-mu-activated B cells after depletion of IL2. In addition, supernatants from some T cell clones, apparently free of IL2 activity, displayed strong BCGF activity in the co-stimulation assay with anti-mu antibody. This BCGF activity was found in 25 kDa fractions by gel filtration and it was unaffected by addition to the cultures of anti-Tac antibody, which consistently inhibited the B cell proliferative response promoted by recombinant IL2. The proliferative response of anti-mu-activated B cells to clonal, IL2-free supernatants containing BCGF and recombinant IL2 present together from the beginning of culture was close to the sum of responses to the two stimulants, separately. In addition, the presence of clonal supernatant containing BCGF from the beginning of culture had a synergistic effect in the response of activated B cells to the subsequent addition of IL2, whereas the initial presence of IL2 had no such an effect on the reactivity of anti-mu-stimulated B cells to the late addition of clonal supernatant containing BCGF. The synergistic effect of BCGF in the IL2-promoted B cell proliferation was probably the result of the recruitment of a greater number of IL2-reactive B cells. In fact, the number of Tac-positive cells was significantly higher in 36-h cultures established in the presence of anti-mu antibody plus clonal supernatant containing BCGF than in cultures stimulated with anti-mu antibody alone. Taken together, these data indicate that anti-mu antibody promotes the expression by normal human B cells of distinct receptors for IL2 and a BCGF distinct from IL2. They also suggest that BCGF can exert a synergistic effect in the IL2-promoted proliferation of activated B cells.