HUMORAL IMMUNE-RESPONSES IN CD40 LIGAND-DEFICIENT MICE

Individuals with X-linked hyper-IgM syndrome fail to express functiona l CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mi ce exhibited no gross developmental deficiencies or health abnormaliti es and contained normal percentages of B and T cell subpopulations. CD 40L-deficient mice did display selective deficiencies in humoral immun ity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-defi cient mice failed to mount secondary antigen-specific responses to imm unization with a thymus-dependent antigen, trinitrophenol-conjugated k eyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient m ice produced antigen-specific antibody of all isotypes except IgE in r esponse to the thymus-independent antigen, DNP-Ficoll. These results u nderscore the requirement of CD40L for T cell-dependent antibody respo nses. Moreover, Ig class switching to isotypes other than IgE can occu r in vivo in the absence of CD40L, supporting the notion that alternat ive B cell signaling pathways regulate responses to thymus-independent antigens.