T cell-derived B cell growth factor(s) can induce stimulation of both resting and activated B cells

The effects of a preparation containing partially purified, EL4-derived B cell growth factor(s) (BCGF) on B cell growth and proliferation have been examined by using B lymphocyte subpopulations separated on the basis of size. BCGF was found to maintain and enhance proliferation of a significant proportion of large activated B cells. In contrast, small resting B cells required the presence of BCGF and a second stimulus such as anti-IgM antibody (anti-mu) to be induced to proliferate. This disparity was not due to a lack of an effect of BCGF on small resting B cells. A factor contained within the partially purified EL4 supernatant produced time-dependent increases in cell size and RNA content in all subpopulations. These effects were independent of possible effects due to contaminating lymphokines such as interleukin 2 (IL 2), concanavalin A (Con A), and phorbol myristate acetate (PMA). Nonmitogenic doses of lipopolysaccharide (LPS) failed to show similar effects. Our data suggest that B cells at all levels of in vivo activation are responsive to stimulation by a growth factor present in EL4 supernatant, as manifested by cell growth and RNA synthesis. This activity has not previously been described for BCGF preparations. However, because the partially purified, EL4-derived supernatant used as BCGF in these studies has not been purified to homogeneity, we cannot conclude whether the factors that induce resting B cells to increase in size are the same as the growth factors that synergize with anti-mu to induce B cell proliferation or that maintain the proliferation of activated B cells.