Cathelin-Related Antimicrobial Peptide (CRAMP) regulates B cell IgG1 production (84.13)

Abstract

Abstract CRAMP belongs to the cathelicidin gene family, which has direct antimicrobial activity against a broad spectrum of microorganisms. Previous studies have shown that CRAMP also modifies the local inflammatory response and regulates cellular and adaptive immunity. However, a possible direct effect of CRAMP on B cells has not been studied. Using CRAMP-deficient mice, we investigated whether B cells express and respond to CRAMP. We show that all mouse B cell subsets tested, including marginal zone, follicular, B1a, and B1b cells, produced CRAMP mRNA directly ex vivo and up-regulate CRAMP upon activation. Purified CRAMP-deficient B cells produced less IgG1 in response to CD40L or LPS plus IL-4 when compared to WT B cells, and the addition of exogenous CRAMP restored the level of IgG1. CRAMP-deficiency had no effect on proliferation, survival, or class switch recombination, but resulted in a decrease in the amount of mature IgG1 mRNA and single cell IgG1 production. Surprisingly, immunization with TNP-OVA with alum resulted in an enhanced TNP-specific IgG1 memory response in CRAMP-deficient mice compared to WT B6 mice. ELISpot and PCR analysis revealed increased numbers of TNP-specific IgG1-secreting B cells and increased CD4+ T cell IL-4 expression in CRAMP-deficient mice. Taken together these results show that B cells express and respond to CRAMP positively in vitro while in vivo CRAMP appears to also indirectly alter B cells through modulation of T cell cytokine production.