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.

抗原刺激（信号1）触发B细胞增殖并引发B细胞募集，参与并响应T细胞帮助（信号2）。在定义的时间窗口内未接收到信号2会导致B细胞凋亡，但对依赖共刺激的机制尚不完全清楚。Nr4a1 – 3编码一小部分孤儿核受体，这些受体被B细胞抗原受体刺激迅速诱导。在这里，我们表明，NR4A1和NR4A3在没有共同刺激的情况下，发挥部分多余的作用来抑制B细胞对抗原的反应，并部分地通过抑制BATF和MYC的表达来发挥作用。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。此类NR4A介导的调节在竞争条件下特别发挥作用，以限制T细胞的帮助。