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J Exp Med. 2004 Jul 5;200(1):115-22. Epub 2004 Jun 28.

Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.

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1
Department of Internal Medicine/Rheumatology, Washington University School of Medicine, Campus Box 8045, CSRB 6617, 660 S. Euclid Ave., St. Louis, MO 63110, USA.

Abstract

B cell terminal differentiation involves development into an antibody-secreting plasma cell, reflecting the concerted activation of proplasma cell transcriptional regulators, such as Blimp-1, IRF-4, and Xbp-1. Here, we show that the microphthalmia-associated transcription factor (Mitf) is highly expressed in naive B cells, where it antagonizes the process of terminal differentiation through the repression of IRF-4. Defective Mitf activity results in spontaneous B cell activation, antibody secretion, and autoantibody production. Conversely, ectopic Mitf expression suppresses the expression of IRF-4, the plasma cell marker CD138, and antibody secretion. Thus, Mitf regulates B cell homeostasis by suppressing the antibody-secreting fate.

PMID:
15226356
PMCID:
PMC2213314
DOI:
10.1084/jem.20040612
[Indexed for MEDLINE]
Free PMC Article
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