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.

中文翻译：

---

Zeb2 驱动 CD11c + 非典型 B 细胞的形成，以维持控制持续感染的生发中心

CD11c+非典型 B 细胞 (ABC) 是另一种与免疫、感染和自身免疫相关的记忆 B 细胞谱系。然而，驱动 ABC 转录程序的因素尚未确定，并且该群体的功能仍未完全了解。在这里，我们根据人类扁桃体 B 细胞单细胞数据集确定了与 ABC 群体相关的候选转录因子。我们鉴定出CD11c+小鼠 B 细胞与人类 ABC 具有相似的转录组特征，并使用优化的 CRISPR-Cas9 敲除筛选，我们观察到锌指 E-box 结合同源盒 2 (Zeb2) 的缺失会损害 ABC 的形成。此外，ZEB2 单倍体不足的 Mowat Wilson 综合征 (MWS) 患者血液中循环 ABC 减少。在镉23创/+泽布2液量/液量 ABC 形成受损的小鼠，ABC 对于有效的体液反应来说是可有可无的疟原虫但需要子孢子免疫来控制复发性血期疟疾。免疫表型分析显示，ABC 驱动最佳的滤泡辅助 T (Tfh) 细胞形成和生发中心 (GC) 反应，并且它们驻留在红/白牙髓边界，可能允许更好地接触病原体抗原进行呈递。总的来说，我们的研究表明 ABC 的形成依赖于 Zeb2，并且这些细胞可以通过维持 GC 反应来限制复发感染。