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

Abstract

Marginal zone (MZ) B cells are innate‐like B cells that produce polyreactive 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 pneumoniae and are also implicated in inflammatory syndromes including lupus erythematosus. The intestinal microbiota is responsible for producing short‐chain fatty acids, which can regulate immune cell function by several mechanisms including ligation of the G‐protein‐coupled receptor (GPR)43. Herein, we show that MZ B cells express Gpr43 messenger RNA 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 titers 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 immunoglobulin M 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 a result of impaired regulation of MZ B cells.

CD6 deficiency impairs early immune response to bacterial sepsis

“…Spleen B1a and MZB cells are considered the main source of natural polyreactive antibodies (NAbs), which in turn are known to play an important role in the innate immune response against bacterial infection ( Aziz et al., 2015 ; Rohrbeck et al., 2021 ; Zhou et al., 2007 ). On this basis, in vitro and in vivo production of anti-dinitrophenol (DNP) antibodies—a surrogate for NAbs ( Gunti et al., 2015 )—was investigated in Cd6 −/ − mice of C57BL/6 background.…”

“…Importantly, our results show that Cd6 −/− mice’s decreased levels of NAbs involve not only IgM but also IgA and some IgG subclasses, which imply involvement of B cells able to undergo class-switch recombination events. NAbs of IgM class have long been associated not only with B1a cells ( Baumgarth et al., 1999 , 2000 ; Chou et al., 2009 ; Thurnheer et al., 2003 ) but also with MZB cells ( Palm and Kleinau, 2021 ; Rohrbeck et al., 2021 ). Nevertheless, it has been recently claimed that most serum IgM in resting mice is produced by a discrete subset of bone marrow resident CD5 − IgM plasma cells originated from fetal-lineage progenitors residing in the peritoneal cavity (neither B1a nor B1b) ( Reynolds et al., 2015 ).…”

Fatty acids role in multiple sclerosis as “metabokines”

“…Low dose generates miRNAs boosting antibody class switch and recombination, yielding more antibodies, while high dose produces a large number of miRNAs targeting Aicda and Prdm1, thus inhibiting class switch and the generation of systemic antigen-specific antibodies [78]. SCFA, by activating GPR43 which is highly expressed among marginal zone B cells, would putatively inhibit antibody production against non-T cell-dependent antigens [123]. In addition, valerate can induce IL-10 production of Breg cells so as to relieve EAE symptoms and infiltration of inflammatory cells [103] (Figs.…”

Strategies for the Identification and Assessment of Bacterial Strains with Specific Probiotic Traits

“…The production of several microbiota metabolites such as SCFAs, required for T-cell induction and metabolism [ 96 , 97 ] and the generation of tolerogenic cytokines [ 98 ], are also thought to be necessary for the identification of novel probiotics for FA. It is now known that these processes are also linked with GPR43 [ 99 ] through the activation of mTOR and STAT3 and epigenetic modifications via inhibition of histone deacetylases, and through the antigen response by marginal-zone B-cell lymphocytes [ 100 ]. STAT 3 is known to enhance allergic reactions [ 101 ] through a significant decrease in cytokines and chemical-released mediators assessed in murine and human mast cells.…”