Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ B-cell responses

Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity Splenic marginal zone B cells are Important producers of autoantibodies and are subject to stringent tolerance mechanisms to prevent autoimmunity In this paper we explore the role of the Mer tyrosine kinase (Mertk) in regulating autoreactive B cells This receptor tyrosine kinase serves to bind apoptotic cells to mediate their phagocytosis and to regulate subsequent cytokine production Mice lacking Mertk suffer from impaired apoptotic cell clearance and develop a lupus-like autoimmune syndrome Here we show that such Mertk-KO mice have expanded numbers of splenic marginal zone B cells Mertk-KO mice bearing a DNA-specific immunoglobulin heavy-chain transgene (3H9) produced anti-DNA antibodies that appeared to be secreted largely by marginal zone B cells Finally Mertk-KO mice developed greater antibody responses after NP-Ficoll immunization than their B6 counterparts Taken together our data show that Mertk has a major effect on the development of the marginal zone B-cell compartment Mertk is also important in establishing DNA-specific B-cell tolerance in 3H9 anti-DNA transgenic mice (c) 2010 Elsevier Ltd All rights reserved