Cytoskeleton Protein 4.1R Regulates B cell fate by Modulating the Canonical NF-κB Pathway.

During the immune response, B cell fate can enter the memory pathway characterized by class switch recombination (CSR) or undergo plasma cell differentiation (PCD) to secrete immunoglobulin (Ig). Both of these processes occur in activated B cells, which are reported relate to membrane-association proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, involves in many cell events such as cell activation, differentiation, and cytokine secretion. However, the effect of 4.1R on regulating B cell fate is still unclear. Here, we show an important association between B cell fate and 4.1R. In vitro, primary B cells were stimulated by LPS combined with IL-4, results showed that 4.1R deficiency (4.1R-/- ) compared with wild type (4.1R+/+ ) B cell augment expression of activation-induced cytidine deaminase (AID) and germline, resulting in increased IgG1+ B cells, whereas, the secretion of IgG1 and IgM were reduced, and interestingly CD138+ B cells were also decreased. Mechanism analysis, during the whole process, 4.1R regulates canonical NF-κB rather than non-canonical NF-κB to promote the expression of CSR complex components leads to up-regulates B cell CSR. On the other hand, 4.1R-deficient B cells showed reduced expression of Blimp-1, which caused B cells to downregulate PCD. Furthermore, over-activation of canonical NF-κB may induce apoptosis signaling to cause PCD apoptosis to reduce the PCD number. In summary, our results suggest that 4.1R acts as a B cell fate regulator via inhibiting the canonical NF-κB signaling pathway.