B cell-intrinsic expression of the RNA-binding protein HuR is essential for humoral immunity by facilitating B-T communication in the lymphoid follicle. (IRM12P.645)

Abstract

Abstract Post-transcriptional regulation of gene expression is critical for the survival, differentiation, and function of B lymphocytes. To investigate roles of the RNA-binding protein HuR in B cells, we generated mice with B-cell specific deletion of HuR using Cre recombinase driven by the Mb1 promoter. These mice have modestly reduced numbers of naïve B cells, but show profound loss of serum antibodies of all isotypes and low numbers of germinal center B cells, plasma cells, and switched memory cells. Further, these mice fail to form germinal centers or undergo affinity maturation upon immunization with NP-OVA. In contrast, HuR-deficient B cells survive, proliferate, class switch, and undergo typical gene expression changes upon in vitro stimulation. We find that HuR regulates expression of CD81, CD70, and CD86, which promote the ability of B cells to physically interact with T cells. Biochemically, HuR binds to mRNAs of genes involved in cytoskeletal remodeling upon B cell activation. Because cytoskeletal reorganization is critical for antigen internalization, these data suggest that HuR-deficient B cells may have an antigen presentation defect. Consistent with the notion that B cell-intrinsic functions of HuR promote B-T communication in vivo, mice with HuR-deficient B cells have reduced numbers of T follicular helper cells, whose differentiation and maintenance are dependent on interactions with B cells. In sum, we find that HuR has critical roles in B cell function.