Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Division of Rheumatology, Rosalind Russell and Ephraim P. Engleman Rheumatology Research Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.
Cell Rep. 2021 Aug 31;36(9):109645. doi: 10.1016/j.celrep.2021.109645.
B cell clones compete for entry into and dominance within germinal centers (GCs), where the highest-affinity B cell receptors (BCRs) are selected. However, diverse and low-affinity B cells can enter and reside in GCs for extended periods. To reconcile these observations, we hypothesize that a negative feedback loop may operate within B cells to preferentially restrain high-affinity clones from monopolizing the early GC niche. Here, we report a role for the nuclear receptor NUR77/Nr4a1 in this process. We show that NUR77 expression scales with antigen stimulation and restrains B cell expansion. Although NUR77 is dispensable for regulating GC size when GCs are elicited in a largely clonal manner, it serves to curb immunodominance under conditions where diverse clonal populations must compete for a constrained niche. We propose that this is important to preserve early clonal diversity in order to limit holes in the post-immune repertoire and to optimize GC selection.
B 细胞克隆在生发中心（GC）中竞争进入和主导地位，在那里选择最高亲和力的 B 细胞受体（BCR）。然而，多样化和低亲和力的 B 细胞可以在 GC 中进入并长时间存在。为了解决这些观察结果，我们假设 B 细胞内可能存在负反馈回路，以优先限制高亲和力克隆垄断早期 GC 生态位。在这里，我们报告了核受体 NUR77/Nr4a1 在这个过程中的作用。我们表明，NUR77 的表达与抗原刺激成正比，并抑制 B 细胞的扩增。虽然当 GC 以主要克隆方式引发时，NUR77 对于调节 GC 大小是可有可无的，但在必须竞争有限生态位的多种克隆群体的情况下，它有助于抑制免疫优势。我们提出，这对于保持早期克隆多样性很重要，以限制免疫后受体库中的空白，并优化 GC 选择。
