当第二信号缺失或受限时，NR4A核受体抑制B细胞对抗原的反应，这一成果由美国加州大学Julie Zikherman课题组经过不懈努力而取得。相关论文于2020年8月31日发表于《自然-免疫学》杂志。

研究人员发现不存在共刺激的情况下，在调节B细胞对抗原反应时Nr4a1和Nr4a3功能存在部分冗余，并且这部分是通过抑制BATF的表达，以及最终抑制MYC的表达完成的。NR4A家族还通过抑制T细胞趋化因子CCL3和CCL4以及CD86和ICAM1的表达来限制B细胞获得T细胞帮助。这种NR4A介导的调控特别是在竞争性限制T细胞帮助时发挥功能。

据介绍，抗原刺激（信号1）诱导B细胞增殖并招募B细胞，参与并响应T细胞帮助（信号2）。在有限时间范围内未接收到信号2的 B细胞会发生凋亡，但尚不完全清楚这种共刺激依赖性的机制。Nr4a1-3编码孤儿核受体家族，其在B细胞抗原受体刺激后迅速产生。

附：英文原文

Title: NR4A nuclear receptors restrain B cell responses to antigen when second signals are absent or limiting

Author: Corey Tan, Ryosuke Hiwa, James L. Mueller, Vivasvan Vykunta, Kenta Hibiya, Mark Noviski, John Huizar, Jeremy F. Brooks, Jose Garcia, Cheryl Heyn, Zhongmei Li, Alexander Marson, Julie Zikherman

Issue&Volume: 2020-08-31

Abstract: 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.

DOI: 10.1038/s41590-020-0765-7

Source: https://www.nature.com/articles/s41590-020-0765-7