title: Disrupted Mer receptor tyrosine kinase expression leads to enhanced MZ B-cell responses.
abstract: 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.
authors.affiliation: Section of Rheumatology, Department of Medicine, Temple University, USA.
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Shao
authors.forename: Anita P
authors.initials: AP
authors.lastname: Kuan
authors.forename: Charlie
authors.initials: C
authors.lastname: Wang
authors.forename: Valsamma
authors.initials: V
authors.lastname: Abraham
authors.forename: Meryl A
authors.initials: MA
authors.lastname: Waldman
authors.forename: Antje
authors.initials: A
authors.lastname: Vogelgesang
authors.forename: Gretel
authors.initials: G
authors.lastname: Wittenburg
authors.forename: Arpita
authors.initials: A
authors.lastname: Choudhury
authors.forename: Patricia Y
authors.initials: PY
authors.lastname: Tsao
authors.forename: Takashi
authors.initials: T
authors.lastname: Miwa
authors.forename: Robert A
authors.initials: RA
authors.lastname: Eisenberg
authors.forename: Philip L
authors.initials: PL
authors.lastname: Cohen
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D000076202:c-Mer Tyrosine Kinase
chemical_list: D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D011518:Proto-Oncogene Proteins; C490767:Mertk protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase
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