In addition, it is becoming increasingly appreciated that AMPs are also immunomodulatory. For example, AMPs have been shown to act as chemoattractants 3–5, protect skin and mucosal surfaces against bacterial infections 6–10, promote wound healing 11–13, and modulate changes in cellular function 14–18. The mechanism by which AMPs modulate immune trafficking and function is not completely understood, although a number of potential receptors have been suggested for the human cathelicidin LL-37. These include EGFR 11, 13, 19, FPRL1 3, 5, P2X720, 21, GAPDH 22, and CXCR2 23. The mouse cathelin-related antimicrobial peptide (mCRAMP) is encoded by the gene Camp and is the sole identified mouse cathelicidin. Camp

is the mouse ortholog of the only human cathelicidin gene (CAMP), which encodes the peptide LL-37 24. mCRAMP forms a positively charged amphipathic α-helical structure 25, 26 and has direct antimicrobial Ferrostatin-1 order properties through a number of proposed mechanisms 27. While mCRAMP and other AMPs have been studied mainly for their role in regulating innate cell activation, their role

in the adaptive immune response has been studied less extensively. LL-37 is expressed in human B and T cells 4, 28; however, mCRAMP expression in mouse lymphocytes has not been investigated. Mature B cells play an important role in the adaptive immune response through check details antigen presentation, T-cell-independent (TI) and -dependent (TD) antibody production, and regulatory functions 29, 30. A TD antibody response is a tightly regulated process that needs T- and B-cell cooperation for an optimal antibody response. T-cell membrane-bound CD40L and secreted IL-4 interact with B-cell membrane-bound CD40 and IL-4R, respectively, to induce class switching to IgG1 31, 32 and IgE 33, which are important antibody isotypes produced in a wide variety of immune responses. The ability of mouse B and T cells to produce and respond to mCRAMP and its role in an adaptive immune response is not fully known. We hypothesized

that mouse B and T cells express and respond to mCRAMP. In the current study, we show that all mature B-cell subsets tested, including marginal zone (MZ), follicular (FO), B1a, and B1b cells as well as all mature T-cell subsets tested express Camp mRNA and mCRAMP protein directly ex vivo. Camp mRNA Histone demethylase was rapidly upregulated in mouse B and T cells following activation. Purified Camp−/− B cells produced equivalent levels of IgM, IgG3, and IgG2c but less IgG1 and IgE, while purified Camp−/− CD4+ T cells cultured in Th2-inducing conditions produced more IL-4+ cells when compared with WT B and T cells, effects that were reversed upon addition of exogenous mCRAMP. In addition, immunization of Camp−/− mice with TNP-OVA, a TD antigen, showed an enhanced TNP-specific secondary IgG1 antibody response, increased IgG1 antibody-secreting cells (ASCs), and increased IL-4-producing T cells.