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Role of Id proteins in B lymphocyte activation: new insights from knockout mouse studies

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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.

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Abbreviations

AID :

Activation-induced cytidine deaminase

BCR :

B cell receptor

bHLH :

Basic helix-loop-helix transcription

BMP :

Morphogenic protein

CSR :

Class switch recombination

GLT :

Germline transcription

Id :

Inhibitor of differentiation

IL :

Interleukin

SHM :

Somatic hypermutation

STAT :

Signal transducer and activator of transcription

TGF :

Transforming growth factor

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Acknowledgements

We thank Drs. T. Katakai and T. Kusunoki for critical reading of the manuscript.

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Authors and Affiliations

  1. Center for Molecular Biology and Genetics, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, 606-8507, Kyoto, Japan

    Manabu Sugai, Hiroyuki Gonda, Yukiko Nambu & Akira Shimizu

  2. Translational Research Center, Kyoto University Hospital, 54 Shogoin-Kawahara-cho, Sakyo-ku, 606-8507, Kyoto, Japan

    Hiroyuki Gonda & Akira Shimizu

  3. Department of Molecular Genetics, School of Medicine, University of Fukui, 23 Shimoaizuki, Matsuoka, 910-1193, Fukui, Japan

    Yoshifumi Yokota

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  1. Manabu Sugai
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  2. Hiroyuki Gonda
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Correspondence to Manabu Sugai.

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Sugai, M., Gonda, H., Nambu, Y. et al. Role of Id proteins in B lymphocyte activation: new insights from knockout mouse studies. J Mol Med 82, 592–599 (2004). https://doi.org/10.1007/s00109-004-0562-z

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