The transcription factor ZEB2 drives the formation of age-associated B cells

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…

• NN
  National Natural Science Foundation of China

  Awards: 81901637, 82071843, 2005DKA21300, 31930037, 31630021
• SP
  Sanming Project of Medicine in Shenzhen

  Award: SZSM201602087