Abstract
B lymphocyte development and function depend upon the activity of intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are interpreted, amplified, fine-tuned, or suppressed through the precise actions of specialized cell surface coreceptors, or "response regulators," that inform B cells of their extracellular environment. Important cell surface response regulators include the CD19/CD21 complex, CD22, and CD72. CD19 establishes a novel Src-family protein tyrosine kinase (PTK) amplification loop that regulates basal signaling thresholds and intensifies Src-family PTK activation following BCR ligation. In turn, CD22 limits the intensity of CD19-dependent, BCR-generated signals through the recruitment of potent phosphotyrosine and phosphoinositide phosphatases. Herein we discuss our current understanding of how CD19/CD21 and CD22 govern the emergence and intensity of BCR-mediated signals, and how alterations in these tightly controlled regulatory activities contribute to autoimmunity in mice and humans.
Publication types
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Antigens, CD19 / chemistry
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Antigens, CD19 / genetics
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Antigens, CD19 / metabolism*
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Antigens, Differentiation, B-Lymphocyte / chemistry
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / metabolism*
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Autoimmunity
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B-Lymphocytes / immunology*
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Cell Adhesion Molecules*
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Humans
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Lectins*
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Lymphocyte Activation
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Mice
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Mice, Knockout
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Models, Immunological
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Receptors, Antigen, B-Cell / metabolism
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Receptors, Complement 3d / chemistry
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Receptors, Complement 3d / genetics
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Receptors, Complement 3d / metabolism*
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Sialic Acid Binding Ig-like Lectin 2
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Signal Transduction
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src-Family Kinases / metabolism
Substances
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Antigens, CD
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Antigens, CD19
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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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Lectins
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Receptors, Antigen, B-Cell
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Receptors, Complement 3d
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Sialic Acid Binding Ig-like Lectin 2
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src-Family Kinases