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The development, activation and differentiation of T and B lymphocytes are regulated by the best characterized PI3K\u2010PI (3,4,5) P3\u2010AKT 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 <jats:italic>Inpp4b<\/jats:italic> was highly expressed in human and murine T\u2010 and B\u20101 lymphocytes. Despite its higher expression in T lymphocytes, neither T cell development and homeostasis nor in vitro T cell activation and CD4<jats:sup>+<\/jats:sup> T cell differentiation were altered upon loss of <jats:italic>Inpp4b<\/jats:italic>. Interestingly, combined direct phenotype analysis of <jats:italic>Inpp4b<\/jats:italic> conventional knockout mice and adoptive transfer studies revealed that ablation of <jats:italic>Inpp4b<\/jats:italic> intrinsically reduced peritoneal B\u20101 cells rather B\u20102 cells. Moreover, <jats:italic>Inpp4b<\/jats:italic> deficiency led to impaired thymus independent (TI) and thymus dependent (TD) antigens\u2010induced antibody production. Further in vitro analysis revealed that CD40\u2010mediated B cell proliferation was impaired upon ablation of <jats:italic>Inpp4b<\/jats:italic>. Our findings reveal that Inpp4b is required in regulating B\u20101 cell numbers and B cell\u2010mediated antibody production.<\/jats:p>","DOI":"10.1111\/sji.13309","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T14:35:37Z","timestamp":1688135737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Regulation of B\u20101 cell numbers and B cell\u2010mediated antibody production by Inpp4b"],"prefix":"10.1111","volume":"98","author":[{"given":"Meizhen","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism Xuzhou Medical University  Xuzhou China"},{"name":"National Experimental Demonstration Center for Basic Medicine Education Xuzhou Medical University  Xuzhou China"},{"name":"Clinical Laboratory Center The First Hospital of Putian City  Putian 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