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

The Journal of Experimental Medicine
Ling LinStanford L Peng

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.

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Methods Mentioned

BETA
PCR
FCS
Assay
dissecting
Genotyping
flow cytometry
ELISA
transfection
electrophoretic mobility shift

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