| First Author | Dai D | Year | 2024 |
| Journal | Science | Volume | 383 |
| Issue | 6681 | Pages | 413-421 |
| PubMed ID | 38271512 | Mgi Jnum | J:353559 |
| Mgi Id | MGI:7577532 | Doi | 10.1126/science.adf8531 |
| Citation | Dai D, et al. (2024) The transcription factor ZEB2 drives the formation of age-associated B cells. Science 383(6681):413-421 |
| abstractText | Age-associated B cells (ABCs) accumulate during infection, aging, and autoimmunity, contributing to lupus pathogenesis. In this study, we screened for transcription factors driving ABC formation and found that zinc finger E-box binding homeobox 2 (ZEB2) is required for human and mouse ABC differentiation in vitro. ABCs are reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with toll-like receptor 7 (TLR7)-driven lupus, ZEB2 is essential for ABC formation and autoimmune pathology. ZEB2 binds to +20-kb myocyte enhancer factor 2b (Mef2b)'s intronic enhancer, repressing MEF2B-mediated germinal center B cell differentiation and promoting ABC formation. ZEB2 also targets genes important for ABC specification and function, including Itgax. ZEB2-driven ABC differentiation requires JAK-STAT (Janus kinase-signal transducer and activator of transcription), and treatment with JAK1/3 inhibitor reduces ABC accumulation in autoimmune mice and patients. Thus, ZEB2 emerges as a driver of B cell autoimmunity. |
