Abstract
Lyn-deficient mice were generated to analyze the role of Lyn in B cell antigen receptor (BCR) signaling. These mice had a reduced number of peripheral B cells with a greater proportion of immature cells and a higher than normal turnover rate. Aged lyn-/- mice developed splenomegaly, produced autoantibodies, and had an expanded population of B lymphoblasts of the B1 lineage. Splenic B cells from young lyn-/- mice initiated early BCR signaling events, although in a delayed fashion. Unexpectedly, lyn-/- B cells exhibited an enhanced MAP kinase activation and an increased proliferative response to BCR engagement. Stimulation of lyn-/- B cells with intact and F(ab')2 anti-IgM revealed defects in at least two mechanisms that negatively regulate BCR signaling, one of which involves Fc gammaRIIb1.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / genetics
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Aging / immunology
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Animals
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Antibodies, Anti-Idiotypic / metabolism
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Antigens, CD / biosynthesis
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Autoantibodies / metabolism
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B-Lymphocytes / cytology
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B-Lymphocytes / enzymology*
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B-Lymphocytes / metabolism
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B7-2 Antigen
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Chickens
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Down-Regulation*
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins / biosynthesis
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Mice
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Phenotype
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Phosphorylation
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Pseudogenes
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Receptors, IgG / metabolism
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Signal Transduction*
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Surface Properties
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Tyrosine / metabolism
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src-Family Kinases / deficiency
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src-Family Kinases / genetics
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src-Family Kinases / metabolism*
Substances
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Antibodies, Anti-Idiotypic
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Antigens, CD
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Autoantibodies
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B7-2 Antigen
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Cd86 protein, mouse
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Lipopolysaccharides
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Membrane Glycoproteins
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Receptors, IgG
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anti-IgM
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Tyrosine
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lyn protein-tyrosine kinase
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src-Family Kinases
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Calcium-Calmodulin-Dependent Protein Kinases