Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor.
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.
Lin
Ling
L
Department of Internal Medicine/Rheumatology, Washington University School of Medicine, Campus Box 8045, CSRB 6617, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
Gerth
Andrea J
AJ
Peng
Stanford L
SL
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D050835:Interferon Regulatory Factors; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D051739:Microphthalmia-Associated Transcription Factor; D010950:Plasma Cells / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099218:Interferon Regulatory Factor-4
D000906:Antibodies; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D051739:Microphthalmia-Associated Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D000099218:Interferon Regulatory Factor-4; C497235:Mitf protein, mouse; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2