The role of CD40-CD154 interaction in antiviral T cell-independent IgG responses

Polyomavirus (PyV) infection elicits protective T cell-independent (TI) IgG responses in T cell-deficient mice. The question addressed in this report is whether CD40 signaling plays a role in this TI antiviral IBG response. B ecause CD40 ligand (CD40L) can be expressed on numerous cell types in addit ion to activated T cells, it is possible that cells other than T cells prov ide CD40L to signal through CD40 on B cells and hence positively influence the antiviral TI IgG responses. In this study we show, by blocking CD40-CD4 0L interactions in vivo with anti-CD40L Ab treatment in TCR beta x delta(-/ -) mice and by using SCID mice reconstituted with CD40(-/-) B cells, that t he lack of CD40 signaling in B cells results in a 50% decrease in TI IgG se creted in response to PyV, SCID mice reconstituted with CD40L(-/-) B cells also responded to PyV infection with diminished IgG secretion compared with that of SCID mice reconstituted with wild-type B cells. This finding sugge sts that B cells may provide the CD40L for CD40 signaling in the absence of T cell help during acute virus infection. Our studies demonstrate that, al though about half of the TI IgG responses to PyV are independent of CD40-CD 40L interactions, these interactions occur in T cell-deficient mice and enh ance antiviral TI Ab responses.