Abstract
FcR specific for pentameric IgM (FCMR) is expressed at high levels by B cells. Although circulating IgM has profound effects on responses to pathogens, autoimmunity, and B cell homeostasis, the biologic consequences of its binding to FCMR are poorly understood. We interrogated FCMR contributions to B cell function by studying mice that lack FCMR. FCMR transcripts are expressed at different levels by various B cell subsets. FCMR-deficient mice have reduced numbers of developing B cells, splenic follicular and peritoneal B-2 cells, but increased levels of peritoneal B-1a cells and autoantibodies. After immunization, germinal center B cell and plasma cell numbers are increased. FCMR-deficient B cells are sensitive to apoptosis induced by BCR ligation. Our studies demonstrate that FCMR is required for B cell differentiation and homeostasis, the prevention of autoreactive B cells, and responsiveness to antigenic challenge.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Antibody Formation / immunology
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Antigens / immunology*
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Apoptosis / immunology
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Autoimmunity / immunology
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology
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Biopolymers
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Bone Marrow / immunology
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Bone Marrow / pathology
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Germinal Center / pathology
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Homeostasis / immunology
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Immunization
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Immunoglobulin M / immunology*
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Immunologic Deficiency Syndromes / genetics
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Immunologic Deficiency Syndromes / immunology*
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Immunologic Deficiency Syndromes / pathology
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Immunologic Memory
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Lymphopoiesis / immunology*
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Mice
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Mice, Inbred C57BL
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Peritoneum / immunology
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Peritoneum / pathology
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Plasma Cells / pathology
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RNA, Messenger / biosynthesis
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Receptors, Antigen, B-Cell / immunology
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Receptors, Fc / biosynthesis
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Receptors, Fc / deficiency
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Receptors, Fc / genetics
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Receptors, Fc / immunology*
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Spleen / immunology
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Spleen / pathology
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T-Lymphocytes / immunology
Substances
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Antigens
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Biopolymers
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Immunoglobulin M
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RNA, Messenger
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Receptors, Antigen, B-Cell
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Receptors, Fc
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immunoglobulin M receptor
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polymeric IgM