Abstract
We have defined roles for the hemopoietic-specific Rho guanosine triphosphatase, Rac2, in B lymphocyte development and function through examination of rac2(-/-) mice. Rac2-deficient mice displayed peripheral blood B lymphocytosis and marked reductions in peritoneal cavity B-1a lymphocytes, marginal zone B lymphocytes, and IgM-secreting plasma cells as well as reduced concentrations of serum IgM and IgA. The rac2(-/-) B lymphocytes exhibited reduced calcium flux following coligation of B cell AgR and CD19 and reduced chemotaxis in chemokine gradients. T cell-independent responses to DNP-dextran were of reduced magnitude, but normal kinetics, in rac2(-/-) mice, while T-dependent responses to nitrophenyl-keyhole limpet hemocyanin were subtly abnormal. Rac2 is therefore an essential element in regulating B lymphocyte functions and maintaining B lymphocyte populations in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / antagonists & inhibitors
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Actins / metabolism
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Animals
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Antibody-Producing Cells / pathology
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Antigens, CD19 / immunology
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Antigens, CD19 / metabolism
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Antigens, T-Independent / pharmacology
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism*
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B-Lymphocyte Subsets / pathology
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Calcium / antagonists & inhibitors
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Calcium / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Migration Inhibition
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Chemokines / pharmacology
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Chemotaxis, Leukocyte / immunology*
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Down-Regulation / genetics
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Down-Regulation / immunology
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Haptens
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Hemocyanins / pharmacology
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Immunoglobulin A / blood
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Immunoglobulin G / biosynthesis
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Immunoglobulin G / blood
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Immunoglobulin M / blood
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Ligands
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Lymphocyte Activation / genetics
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Lymphopenia / genetics
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Lymphopenia / immunology
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Lymphopenia / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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RAC2 GTP-Binding Protein
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Receptors, Antigen, B-Cell / metabolism*
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Receptors, Antigen, B-Cell / physiology
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Up-Regulation / genetics
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Up-Regulation / immunology
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rac GTP-Binding Proteins / deficiency
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / physiology*
Substances
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4-hydroxy-3-nitrophenylacetyl-keyhole limpet hemocyanin
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Actins
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Antigens, CD19
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Antigens, T-Independent
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Chemokines
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Haptens
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Immunoglobulin A
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Immunoglobulin G
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Immunoglobulin M
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Ligands
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Receptors, Antigen, B-Cell
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Hemocyanins
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rac GTP-Binding Proteins
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Calcium