Abstract
In addition to the tyrosines of the Igalpha and beta immunoreceptor tyrosine-based activation motifs (ITAMs), the evolutionarily conserved Igalpha non-ITAM tyrosine 204 becomes phosphorylated upon antigen recognition by the B cell receptor (BCR). Here we demonstrate that splenic B cells from mice with a targeted mutation of Igalpha Y204 exhibited an isolated defect in T cell-independent B cell activation, proliferation, and antibody response upon BCR engagement, yet normal BCR capping, antigen internalization, antigen presentation, and T cell-dependent antibody production. Mutant B cells, present in normal numbers, exhibited unimpaired BCR-induced spleen tyrosine kinase (Syk) phosphorylation but reduced B cell linker protein (BLNK) phosphorylation, calcium flux, and nuclear factor kappaB (NFkappaB), c-jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. These results suggest that Igalpha non-ITAM tyrosine 204 promotes a distinct cellular response, namely T-independent B cell proliferation and differentiation via phosphorylation of the adaptor BLNK.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Sequence
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Animals
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Antigen Presentation / immunology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Calcium / metabolism
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Carrier Proteins / metabolism
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Cell Differentiation
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Cell Proliferation
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Cytoplasm / metabolism*
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Enzyme Activation
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Immunoglobulin alpha-Chains / chemistry*
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Immunoglobulin alpha-Chains / genetics
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Immunoglobulin alpha-Chains / immunology*
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Immunoglobulin alpha-Chains / metabolism
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Intracellular Signaling Peptides and Proteins / metabolism
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Lymphocyte Activation*
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Mice
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Mitogen-Activated Protein Kinases / metabolism
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Molecular Sequence Data
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Mutation / genetics
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NF-kappa B / metabolism
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Phosphoproteins / metabolism
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Phosphorylation
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Protein-Tyrosine Kinases / metabolism
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Receptors, Antigen, B-Cell / chemistry
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology*
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Receptors, Antigen, B-Cell / metabolism
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Syk Kinase
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Tyrosine / genetics
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Tyrosine / metabolism*
Substances
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Adaptor Proteins, Signal Transducing
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B cell linker protein
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Carrier Proteins
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Immunoglobulin alpha-Chains
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Intracellular Signaling Peptides and Proteins
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NF-kappa B
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Phosphoproteins
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Receptors, Antigen, B-Cell
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Tyrosine
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Protein-Tyrosine Kinases
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Syk Kinase
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Syk protein, mouse
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Mitogen-Activated Protein Kinases
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Calcium