Open AccessNR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting
Author(s) -
Chung-I Tan,
Ryosuke Hiwa,
James L. Mueller,
Vivasvan Vykunta,
Kenta Hibiya,
Mark Noviski,
John Huizar,
Jeremy F. Brooks,
José García,
Cheryl S. Heyn,
Zhongmei Li,
Alexander Marson,
Julie Zikherman
Publication year - 2020
Publication title -
nature immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.074
H-Index - 388
eISSN - 1529-2916
pISSN - 1529-2908
DOI - 10.1038/s41590-020-0765-7
Subject(s) - microbiology and biotechnology , nerve growth factor ib , b cell , biology , receptor , antigen , cd86 , nuclear receptor , t cell , stimulation , immunology , transcription factor , neuroscience , antibody , immune system , genetics , gene
Antigen stimulation (signal 1) triggers B cell proliferation and primes B cells to recruit, engage and respond to T cell help (signal 2). Failure to receive signal 2 within a defined time window results in B cell apoptosis, yet the mechanisms that enforce dependence on co-stimulation are incompletely understood. Nr4a1-3 encode a small family of orphan nuclear receptors that are rapidly induced by B cell antigen receptor stimulation. Here, we show that Nr4a1 and Nr4a3 play partially redundant roles to restrain B cell responses to antigen in the absence of co-stimulation and do so, in part, by repressing the expression of BATF and, consequently, MYC. The NR4A family also restrains B cell access to T cell help by repressing expression of the T cell chemokines CCL3 and CCL4, as well as CD86 and ICAM1. Such NR4A-mediated regulation plays a role specifically under conditions of competition for limiting T cell help.