INDUCTION OF B-CELL COSTIMULATORY FUNCTION BY RECOMBINANT MURINE CD40LIGAND

T cell-dependent regulation of B cell growth and differentiation invol ves an interaction between CD40, a B cell surface molecule, and the CD 40 ligand (CD40L) which is expressed on activated CD4(+) T cells. In t he current study, we show that recombinant membrane-bound murine CD40L induces B cells to express costimulatory function for the proliferati on of CD4(+) T cells. CD40L- or lipopolysaccharide (LPS)-activated, bu t not control-cultured B cells were strong costimulators of anti-CD3 o r alloantigen-dependent T cell responses. The molecular interactions r esponsible for the increased costimulatory functions were examined by analyzing the activated B cells for changes in the expression of two c ostimulatory molecules, B7 and heat-stable antigen (HSA), as well as b y the use of antagonists of B7 and HSA (CTLA4.Fc and 20C9, respectivel y). The expression of both B7 and HSA was enhanced on B cells activate d with LPS. As observed in previous studies, the costimulatory activit y of the LPS-activated B cells was dependent on both B7 and HSA and wa s completely inhibited in the presence of a combination of CTLA4.Fe an d 20C9. In contrast, activation of B cells with CD40L induced the expr ession of B7 but did not enhance the expression of HSA. In addition th e costimulatory activity of the CD40L-activated B cells was partially, but not completely, inhibited by the combination of CTLA4.Fc and 20C9 . These results demonstrate that CD40L regulates costimulatory functio n of B cells in part by inducing the expression of B7 and suggest that CD40L-activated B cells express an additional costimulatory activity that is not associated with LPS-activated B cells.