Abstract
Fc receptor-like A (FCRLA) and FCRLB have homology to the transmembrane FCRL family members (FCRL 1-6) and to the conventional receptors for the Fc portion of immunoglobulin, but uniquely are cytosolic proteins expressed in B cells. Here we describe the phenotype of Fcrlb-gene targeted mice. B cell development and in vitro responses are normal; however, antibody responses to a T-dependent antigen are elevated. The gene encoding the inhibitory FcγRIIb is located nearby Fcrlb. Although Fcrlb-gene targeting had no effect on the function or basal expression of FcγRIIb, its expression was reduced following activation. This abnormal regulation was due to co-inheritance of Fcgr2b and the mutant Fcrlb allele from the 129 ES cells. A promoter polymorphism in the 129/Sv Fcgr2b allele results in diminished upregulation of FcγRIIb following B cell activation. Thus, we speculate that the enhanced antibody response seen in the FCRLB-deficient mice may be due to the Fcgr2b promoter.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Anti-Idiotypic / immunology
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Antibodies, Anti-Idiotypic / pharmacology
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Antibodies, Antinuclear / blood
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Antibodies, Antinuclear / immunology
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Antibody Formation / genetics
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Antibody Formation / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Count
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Cell Proliferation / drug effects
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Gene Expression / genetics
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Immunoglobulin Fab Fragments / immunology
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Immunoglobulin Fab Fragments / pharmacology
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / immunology
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Mice
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Mice, 129 Strain
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Mice, Inbred C57BL
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Mice, Knockout
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Nitrophenols / immunology
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Phenylacetates / immunology
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Polymorphism, Genetic / genetics
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Polymorphism, Genetic / immunology
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Promoter Regions, Genetic / genetics
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Receptors, Fc / deficiency*
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Receptors, Fc / genetics
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Receptors, IgG / genetics
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Receptors, IgG / metabolism*
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Vaccination
Substances
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Antibodies, Anti-Idiotypic
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Antibodies, Antinuclear
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Fcgr2b protein, mouse
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Fcrlm2 protein, mouse
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Immunoglobulin Fab Fragments
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Lipopolysaccharides
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Nitrophenols
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Phenylacetates
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Receptors, Fc
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Receptors, IgG
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anti-IgM
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4-hydroxy-5-nitrophenyl acetic acid