生发中心
CD11c公司
生物
免疫学
细胞生物学
遗传学
B细胞
表型
基因
抗体
作者
Xin Gao,Qian Shen,Jonathan A. Roco,Becan Dalton,Katie Frith,C. Mee Ling Munier,Fiona D. Ballard,Ke Wang,Hannah G. Kelly,Maxim Nekrasov,Jin-Shu He,Rebecca Jaeger,Patricia E. Carreira,Julia I. Ellyard,Lynette Beattie,Anselm Enders,Matthew C. Cook,John Zaunders,Ian A. Cockburn
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-02-08
标识
DOI:10.1126/sciimmunol.adj4748
摘要
CD11c + atypical B cells (ABCs) are an alternative memory B cell lineage associated with immunization, infection, and autoimmunity. However, the factors that drive the transcriptional program of ABCs have not been identified, and the function of this population remains incompletely understood. Here we identified candidate transcription factors associated with the ABC population based on a human tonsillar B cell single cell dataset. We identified CD11c + B cells in mice with a similar transcriptomic signature to human ABCs, and using an optimized CRISPR-Cas9 knockdown screen, we observed that loss of zinc finger E-box binding homeobox 2 (Zeb2) impaired ABC formation. Furthermore, ZEB2 haplo-insufficient Mowat Wilson syndrome (MWS) patients have decreased circulating ABCs in the blood. In Cd23 Cre/+ Zeb2 fl/fl mice with impaired ABC formation, ABCs were dispensable for efficient humoral responses after Plasmodium sporozoite immunization but were required to control recrudescent blood-stage malaria. Immune phenotyping revealed that ABCs drive optimal T follicular helper (Tfh) cell formation and germinal center (GC) responses and they reside at the red/white pulp border likely permitting better access to pathogen antigens for presentation. Collectively, our study shows that ABC formation is dependent upon Zeb2, and these cells can limit recrudescent infection by sustaining GC reactions.
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