| First Author | Laidlaw BJ | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 9 | Pages | 1082-1093 |
| PubMed ID | 32601467 | Mgi Jnum | J:299150 |
| Mgi Id | MGI:6490658 | Doi | 10.1038/s41590-020-0713-6 |
| Citation | Laidlaw BJ, et al. (2020) The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development. Nat Immunol 21(9):1082-1093 |
| abstractText | Memory B cells (MBCs) are essential for long-lived humoral immunity. However, the transcription factors involved in MBC differentiation are poorly defined. Here, using single-cell RNA sequencing analysis, we identified a population of germinal center (GC) B cells in the process of differentiating into MBCs. Using an inducible CRISPR-Cas9 screening approach, we identified the hematopoietically expressed homeobox protein Hhex as a transcription factor regulating MBC differentiation. The corepressor Tle3 was also identified in the screen and was found to interact with Hhex to promote MBC development. Bcl-6 directly repressed Hhex in GC B cells. Reciprocally, Hhex-deficient MBCs exhibited increased Bcl6 expression and reduced expression of the Bcl-6 target gene Bcl2. Overexpression of Bcl-2 was able to rescue MBC differentiation in Hhex-deficient cells. We also identified Ski as an Hhex-induced transcription factor involved in MBC differentiation. These findings establish an important role for Hhex-Tle3 in regulating the transcriptional circuitry governing MBC differentiation. |
