Role of Id proteins in B lymphocyte activation: new insights from knockout mouse studies.
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.
Sugai
Manabu
M
Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, 606-8507 Kyoto, Japan. msugai@virus.kyoto-u.ac.jp
Gonda
Hiroyuki
H
Nambu
Yukiko
Y
Yokota
Yoshifumi
Y
Shimizu
Akira
A
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle / Q000502:physiology; D003564:Cytidine Deaminase / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000097:blood; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051757:PAX5 Transcription Factor; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D051792:Basic Helix-Loop-Helix Proteins; D003564:Cytidine Deaminase; D004268:DNA-Binding Proteins; D007073:Immunoglobulin E; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D051757:PAX5 Transcription Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D000098830:AICDA (Activation-Induced Cytidine Deaminase); C497452:Idb2 protein, mouse; C497282:Pax5 protein, mouse; C075668:Tcf3 protein, mouse; C075640:ID3 protein, human