COGNATE T-CELL HELP FOR CD40-DEFICIENT B-CELLS INDUCES C-MYC RNA EXPRESSION, BUT DNA-SYNTHESIS REQUIRES AN ADDITIONAL SIGNAL THROUGH SURFACE IG

To investigate the role of CD40 ligand in the delivery of help to B ce lls, we examined the Ag-specific interaction of B cells from CD40-defi cient mice with a Th2 cell line in vitro, Small resting B cells from n ormal mice are stimulated to synthesize DNA when they present monovale nt Ag (rabbit Fab anti-Ig) to a rabbit Ig-specific Th cell line, This response, which is independent of a signal through the B cell Ag recep tor (sig), is nearly absent in B cells from CD40-deficient mice, The C D40-deficient B cells are not defective in Ag presentation because the y induce T cell IL-4 synthesis as well as normal B cells, Also, CD40-d eficient B cells respond to T cell help with DNA synthesis almost as w ell as normal B cells if an additional signal is provided through sig, In conjunction with a sig signal, cell contact with helper T cells in duces DNA synthesis more effectively than soluble cytokines. CD40-inde pendent T cell help can also be measured as an early increase in c-myc mRNA levels in CD40-deficient B cells presenting Ag to helper T cells , although the levels of c-myc RNA expression are lower than those in normal B cells, However, c-myc RNA induced by noncognate interaction w ith anti-CD3-activated T cells is completely CD40 dependent, We conclu de that early growth signals from activated Th cells are received by C D40(-/-) B cells, but that CD40 and/or slg signals are required for ef ficient induction of DNA synthesis.