The Role of CD40-CD154 Interaction in Antiviral T Cell-Independent IgG Responses

Abstract

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 IgG response. Because CD40 ligand (CD40L) can be expressed on numerous cell types in addition to activated T cells, it is possible that cells other than T cells provide 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-CD40L interactions in vivo with anti-CD40L Ab treatment in TCR β×δ−/− mice and by using SCID mice reconstituted with CD40−/− B cells, that the lack of CD40 signaling in B cells results in a 50% decrease in TI IgG secreted 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 suggests 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, although about half of the TI IgG responses to PyV are independent of CD40-CD40L interactions, these interactions occur in T cell-deficient mice and enhance antiviral TI Ab responses.

B Lymphocyte Activation by Human Papillomavirus-Like Particles Directly Induces Ig Class Switch Recombination via TLR4-MyD88

“…3F), which can be stimulated by CD40L, classically on the surface of Th cells. Significantly, CD40L on the surface of adjacent B cells may provide functional activation of CD40 in Th cell-independent responses (44). Paracrine or autocrine signaling by MIP-1␣, IFN-␣, and IL-6 may regulate the Ab isotypes induced by HPV16 VLP and are consistent with a defense response (35,63,64).…”

MyD88 Is Required for the Formation of Long-Term Humoral Immunity to Virus Infection

“…We previously showed that SCID mice reconstituted with T cell-depleted wild-type splenocytes generated VP1-specific TI IgM and IgG Ab responses after infection with PyV (20). We therefore reconstituted SCID mice with either unfractionated or T cell-depleted wild-type or MyD88 KO splenocytes and measured VP1-specific IgM and IgG Ab responses after PyV infection.…”

“…VP1-specific ELISAs were conducted as previously described (20). Briefly, purified recombinant VP1 protein (0.1 g/ml in carbonate buffer) was used as an immunoadsorbant.…”

Essential Role for CD40 Ligand Interactions in T Lymphocyte-Mediated Modulation of the Murine Immune Response to Pneumococcal Capsular Polysaccharides

“…However, it has also been described that a blocking anti-CD40L Ab (MR1) had little or only modest effect on the antiphosphorylcholine response and that CD40 Ϫ/Ϫ dendritic cells elicited an anti-phosphorylcholine response that was comparable to that observed for wild-type dendritic cells (19). Szomolanyi-Tsuda et al (20) stressed the role of the CD40-CD154 interaction in anti-polyoma virus thymus cell-independent IgG responses. Finally, it has been described 1) that neutralization of CD40L reduced the Ab response to pneumococcal caps-PS elicited by immunization with whole bacteria or with a caps-PS-protein conjugate and 2) that the immune response to a caps-PS-protein conjugate was higher in wild-type mice than in CD40L-deficient mice (21,22).…”