TY - JOUR T1 - Regeneration of humoral immunity from pluripotent stem cells by defined transcription factors JF - bioRxiv DO - 10.1101/2021.07.30.454442 SP - 2021.07.30.454442 AU - Qi Zhang AU - Bingyan Wu AU - Qitong Weng AU - Fangxiao Hu AU - Yunqing Lin AU - Chengxiang Xia AU - Huan Peng AU - Yao Wang AU - Xiaofei Liu AU - Lijuan Liu AU - Jiapin Xiong AU - Yang Geng AU - Yalan Zhao AU - Mengyun Zhang AU - Juan Du AU - Jinyong Wang Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/07/30/2021.07.30.454442.abstract N2 - Regeneration of humoral immunity from pluripotent stem cells (PSCs) is a crucial aim in translational medicine. However, reconstitution of complete, sustained, and functional B lymphopoiesis from PSCs has not yet been developed. Here, we successfully achieved regenerative B lymphopoiesis in B-cell deficient animals transplanted with PSC-derived hematopoietic progenitors (iHPCs) guided by synergistic expression of Runx1, Hoxa9, and Lhx2. Upon transplantation, the iHPCs immediately gave rise to pro/pre-B cells in recipients’ bone marrow, which were able to further differentiate into the entire B cell lineages, including innate B-1a, B-1b, MZ B cells, as well as adaptive FO B cells. In responding to antigen stimuli, the regenerative B cells produced adaptive humoral immune responses, sustained a prolonged antigen-specific antibody production, and formed immune-memory. Particularly, the regenerative B cells in spleen showed developing patterns of immunoglobulin chain-switch and hyper-mutation via a cross-talk with the host T follicular helper cells, which eventually formed T cell-dependent humoral responses. This study provides de novo evidence that B lymphopoiesis can be regenerated from PSCs via a HSC-independent approach, which provides insights into treating B-cell related humoral deficiencies using PSCs as unlimited cell resource.Competing Interest StatementThe authors have declared no competing interest. ER -