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Immunohorizons. 2017 Nov 1;1(9):188-197. doi: 10.4049/immunohorizons.1700048.

Nur77 Is Upregulated in B-1a Cells by Chronic Self-Antigen Stimulation and Limits Generation of Natural IgM Plasma Cells.

Author information

1
Howard Hughes Medical Institute Medical Fellows Program, University of California, San Francisco, San Francisco, CA 94143.
2
Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94143.
3
Rosalind Russell and Ephraim P. Engleman Arthritis Research Center, Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143.

Abstract

B-1a cells are a unique population of innate-like B cells with a highly restricted and self-reactive BCR repertoire. Preimmune "natural" IgM produced by B-1a-derived plasma cells is essential for homeostatic clearance of cellular debris and forms a primary layer of protection against infection. In this study, we take advantage of a fluorescent reporter of BCR signaling to show that expression of the orphan nuclear hormone receptor Nur77 is upregulated under steady-state conditions in self-reactive B-1a cells in response to chronic Ag stimulation. Nur77-deficient mice exhibit elevated natural serum IgM (but not IgG) and marked expansion of IgM plasma cells of B-1a origin. Moreover, we show that Nur77 restrains the turnover of B-1a cells and the accumulation of immature IgM plasma cells. Thus, we identify a new critical negative-regulatory pathway that serves to maintain B-1a cells in a quiescent state in the face of chronic endogenous Ag stimulation.

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