| First Author | Brooks JF | Year | 2021 |
| Journal | Cell Rep | Volume | 36 |
| Issue | 9 | Pages | 109645 |
| PubMed ID | 34469720 | Mgi Jnum | J:316921 |
| Mgi Id | MGI:6765706 | Doi | 10.1016/j.celrep.2021.109645 |
| Citation | Brooks JF, et al. (2021) Negative feedback by NUR77/Nr4a1 restrains B cell clonal dominance during early T-dependent immune responses. Cell Rep 36(9):109645 |
| abstractText | 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. |
