Abstract
Id (inhibitor of differentiation) proteins play important roles in cell differentiation, cell cycle control, and apoptosis. They act as negative regulators of basic helix-loop-helix-type transcription factors, which positively regulate differentiation of various cell types. Id proteins work to block B lymphocyte (B cell) maturation at an early differentiation step, as demonstrated by gain-of-function studies. In recent years a series of gene-targeted mice lacking different Ids have been generated. Analyses of these gene-targeted mice provide information useful for understanding the physiological roles of Ids in B cell biology. Id3 is required for proper B cell functions and acts by controlling the cell cycle. Upon B cell activation, Id2 acts as a negative regulator to prevent potentially harmful effects brought about by excessive immunological reactions; one of its special roles is to maintain low serum concentrations of immunoglobulin E (IgE). The Id2 protein does this by antagonizing E2A and Pax5 activities, both of which are required for proper B cell activation. This review presents several new insights into B cell differentiation and activation programs and the physiological role of Id proteins in B cell activation.
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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Basic Helix-Loop-Helix Transcription Factors
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Cell Cycle / physiology
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Cytidine Deaminase / biosynthesis
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Immunoglobulin Class Switching
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Immunoglobulin E / blood
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Inhibitor of Differentiation Protein 2
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Inhibitor of Differentiation Proteins
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Lymphocyte Activation / physiology*
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Mice
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Mice, Knockout
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Neoplasm Proteins / deficiency
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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PAX5 Transcription Factor
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Repressor Proteins / genetics
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Repressor Proteins / physiology*
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transforming Growth Factor beta / physiology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Idb2 protein, mouse
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Inhibitor of Differentiation Protein 2
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Inhibitor of Differentiation Proteins
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Neoplasm Proteins
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PAX5 Transcription Factor
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Pax5 protein, mouse
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Repressor Proteins
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Tcf3 protein, mouse
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Transcription Factors
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Transforming Growth Factor beta
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ID3 protein, human
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Immunoglobulin E
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AICDA (activation-induced cytidine deaminase)
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Cytidine Deaminase