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¹ Department of Internal Medicine/Rheumatology and ² Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Address correspondence to Stanford L. Peng, Dept. of Internal Medicine/Rheumatology and Dept. of Pathology and Immunology, Washington University School of Medicine, Campus Box 8045, CSRB 6617, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 747-3609; Fax: (314) 454-1091; email: speng{at}im.wustl.edu

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.

Key Words: autoimmunity • antibody secretion • cellular differentiation • immunoglobulin • IRF-4

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