Cutting Edge: Myosin 18A Is a Novel Checkpoint Regulator in B Cell Differentiation and Antibody-Mediated Immunity
| Autor: | Neetu Gupta, Ivan Kosik, Ken Matsui, William M. Baldwin, Michael B. Cheung, Gospel Enyindah-Asonye, Nina Dvorina, Jonathan W. Yewdell |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Immunology Hyperglobulinemia Mice Transgenic Myosins Article Mice 03 medical and health sciences 0302 clinical medicine B cell homeostasis Myosin medicine Animals Immunology and Allergy B cell Mice Knockout B-Lymphocytes biology Antibodies Monoclonal Germinal center Cell Differentiation Immunity Humoral Cell biology medicine.anatomical_structure Humoral immunity biology.protein Female Bone marrow Antibody 030215 immunology |
| Zdroj: | J Immunol |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.2100084 |
| Popis: | We investigated the function of the newly discovered myosin family protein myosin 18A (Myo18A) in Ab-mediated immunity by generating B cell–conditional Myo18A-deficient mice. Myo18A deficiency led to expansion of bone marrow progenitor B cells and mature B cells in secondary lymphoid organs. Myo18A-deficient mice displayed serum IgM hyperglobulinemia and increased splenic IgM-secreting cells, with older mice switching to IgG1 hyperglobulinemia and autoantibody development. Immunization of Myo18A-deficient mice with inactivated influenza virus led to development of more potent neutralizing Abs against the major Ag hemagglutinin, associated with persistent accumulation of Ag-specific germinal center B cells and more Ag-specific bone marrow plasma cells. In vitro stimulation with TLR7 and BCR ligands revealed a greater ability of Myo18A-deficient B cells to differentiate into Ab-secreting cells, associated with higher AID and Blimp-1 expression. Overall, our study demonstrates that Myo18A is a novel negative regulator of B cell homeostasis, differentiation, and humoral immunity. |
| Databáze: | OpenAIRE |
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