Abstract
CD22, a negative regulator of B cell antigen receptor signaling, binds glycoconjugates terminating in alpha2, 6 sialic acid. The physiological ligand(s) for CD22 remain unknown. We asked whether the sialic acid binding domains are necessary for CD22 to function as a negative regulator. We generated two mutants that lack sialic acid binding activity and expressed them in a novel CD22(-/-) murine B cell line. Anti-IgM activated B cells expressing either CD22 mutant had greater Ca(2+) responses than cells expressing wild-type CD22. Each variant also had reduced CD22 tyrosine phosphorylation and Src homology 2 domain-containing protein tyrosine phosphatase-1 association. These data suggest that the alpha2, 6 sialic acid ligand binding activity of CD22 is critical for its negative regulatory functions.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / immunology*
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Antigens, CD / metabolism
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Antigens, Differentiation, B-Lymphocyte / immunology*
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Antigens, Differentiation, B-Lymphocyte / metabolism
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Binding Sites
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Calcium Signaling / physiology*
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Cell Adhesion Molecules*
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Cell Line
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DNA Primers
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Gene Expression Regulation / immunology
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Genetic Vectors
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Humans
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Lectins*
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Mice
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Mutagenesis, Site-Directed
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N-Acetylneuraminic Acid / metabolism*
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Receptors, Antigen, B-Cell / immunology*
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Recombinant Proteins / metabolism
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Retroviridae / genetics
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Sialic Acid Binding Ig-like Lectin 2
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Signal Transduction / immunology
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Transfection
Substances
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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CD22 protein, human
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Cd22 protein, mouse
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Cell Adhesion Molecules
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DNA Primers
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Lectins
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Receptors, Antigen, B-Cell
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Recombinant Proteins
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Sialic Acid Binding Ig-like Lectin 2
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N-Acetylneuraminic Acid