GPR43 regulates marginal zone B cell responses to foreign and endogenous antigens.

Marginal zone (MZ) B cells are innate-like B cells that produce poly-reactive antibodies with an affinity for microbial molecular patterns and carbohydrate ligands. MZ B cells have been shown to be important in mediating immunity to various bacteria including Streptococcus pneuomniae and are also implicated in inflammatory syndromes including lupus erythematosus. The intestinal microbiota is responsible for producing short chain fatty acids (SCFA), which can regulate immune cell function by several mechanisms including ligation of the G-protein coupled receptor, GPR43. Herein, we show that MZ B cells express Gpr43 mRNA and that the absence of this receptor impacts on MZ B cell surface marker expression and antibody production. In T cell-independent responses to the hapten 4-Hydroxy-3-nitrophenylacetic acid (NP), mice deficient in GPR43 displayed higher serum titres of NP-specific antibodies. Moreover, in response to a pneumococcal polysaccharide vaccine, GPR43-deficient mice developed robust serum antibody responses and had markedly increased numbers of splenic antibody-secreting cells, compared with control mice. Finally, serum IgM autoantibodies to double stranded DNA and phosphatidylcholine were increased in resting 10-15 week-old mice lacking GPR43. Taken together, mice lacking GPR43 have heightened antibody responses to T cell-independent antigens, which may be due to impaired regulation of MZ B cells.