Regulation of B cell-mediated immune responses by a PX domain-containing protein

Abstract

Abstract The humoral immunity is mediated by antibodies produced by plasma cells, which are terminally differentiated effector cells of the B cell lineage. The antibody production should be tightly regulated to prevent unwanted responses against self-molecules and efficiently defend the host against foreign antigens. In this study, we aimed to examine the roles of PX domain-containing kinase in B cell-mediated immune responses. PX domain-containing kinase is a cytosolic protein composed of a PX domain, a pseudokinase domain, and a WH2 domain. It is expected that PX domain-containing kinase regulates intracellular trafficking of membrane proteins based on its structural features and previously reported functions. PX domain-containing kinase is most highly expressed in B cells both in humans and mice. Furthermore, several reports indicated that SNPs of the PX domain-containing kinase gene are linked to autoimmune diseases commonly characterized by excessive production of autoantibodies, such as systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. However, the in vivo function of PX domain-containing kinase in immune responses has not been reported. In order to investigate the immunoregulatory functions of PX domain-containing kinase, we firstly generated PX domain-containing kinase-deficient mice. Although PX domain-containing kinase is not essential for the development of immune cells, we found that foreign antigen-induced antibody responses were affected by deletion of PX domain-containing kinase in mice. Currently, we are in the process of uncovering the underlying mechanisms. This study is expected to elucidate the functions of PXK as a novel modulator of antibody-mediated immune responses.