美国加州大学旧金山分校Jason G. Cyster研究团队发现，转录因子Hhex与共抑制因子Tle3协同促进记忆B细胞发育。该项研究成果于2020年6月29日在线发表在《自然—免疫学》上。
Title: The transcription factor Hhex cooperates with the corepressor Tle3 to promote memory B cell development
Author: Brian J. Laidlaw, Lihui Duan, Ying Xu, Sara E. Vazquez, Jason G. Cyster
Abstract: 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.