Regulation of B‐1 cell numbers and B cell‐mediated antibody production by Inpp4b

Abstract

AbstractT and B lymphocytes are crucial players in cellular and humoral immune responses. The development, activation and differentiation of T and B lymphocytes are regulated by the best characterized PI3K‐PI (3,4,5) P3‐AKT phosphoinositide signalling pathway. As a branch of the phosphoinositide signalling pathway, the lipid phosphatase INPP4B inhibits AKT activation through degrading the phosphoinositide signalling messenger PI (3,4) P2. However, the role of Inpp4b in T and B lymphocytes remains elusive. Here, we reported that Inpp4b was highly expressed in human and murine T‐ and B‐1 lymphocytes. Despite its higher expression in T lymphocytes, neither T cell development and homeostasis nor in vitro T cell activation and CD4+ T cell differentiation were altered upon loss of Inpp4b. Interestingly, combined direct phenotype analysis of Inpp4b conventional knockout mice and adoptive transfer studies revealed that ablation of Inpp4b intrinsically reduced peritoneal B‐1 cells rather B‐2 cells. Moreover, Inpp4b deficiency led to impaired thymus independent (TI) and thymus dependent (TD) antigens‐induced antibody production. Further in vitro analysis revealed that CD40‐mediated B cell proliferation was impaired upon ablation of Inpp4b. Our findings reveal that Inpp4b is required in regulating B‐1 cell numbers and B cell‐mediated antibody production.