本期文章：《自然—免疫学》：Online/在线发表

美国芝加哥大学Shabaana A. Khader和美国德克萨斯生物医学研究所西南国家灵长类动物研究中心Deepak Kaushal共同合作，近期取得重要工作进展。他们研究发现抗原特异性B细胞引导T滤泡样辅助细胞进入淋巴滤泡以介导结核分枝杆菌控制。相关研究于2023年4月3日在线发表于《自然—免疫学》杂志上。

由结核分枝杆菌（Mtb）引起的结核病（TB）是全球死亡原因之一。肉芽肿相关淋巴组织（GrALT）与结核病期间的保护作用相关，但其保护机制尚不清楚。在TB期间，T细胞而非B细胞中的转录因子IRF4是产生辅助T细胞的T_H1和T_H17亚群以及卵泡辅助T（T_FH）样细胞反应所必需的。在Mtb感染期间，IRF4⁺ T细胞群共表达转录因子BCL6，CD4⁺ T细胞（CD4^cre）中BCL6（Bcl6^fl/fl）的缺失导致T_FH样细胞减少，GrALT内的定位受损，Mtb负荷增加。

相反，生发中心B细胞、B细胞、产生抗体的浆细胞或表达白细胞介素-10的B细胞上MHC II类表达的缺失并没有增加Mtb的易感性。事实上，抗原特异性B细胞通过程序性细胞死亡1（PD-1）及其配体PD-L1之间的相互作用增强细胞因子的产生，并在GrALT内战略性定位T_FH样细胞，并介导小鼠和猕猴的Mtb控制。

附：英文原文

Title: Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control

Author: Swanson, Rosemary V., Gupta, Ananya, Foreman, Taylor W., Lu, Lan, Choreno-Parra, Jose Alberto, Mbandi, Stanley Kimbung, Rosa, Bruce A., Akter, Sadia, Das, Shibali, Ahmed, Mushtaq, Garcia-Hernandez, Maria de la Luz, Singh, Dhiraj K., Esaulova, Ekaterina, Artyomov, Maxim N., Gommerman, Jennifer, Mehra, Smriti, Zuniga, Joaquin, Mitreva, Makedonka, Scriba, Thomas J., Rangel-Moreno, Javier, Kaushal, Deepak, Khader, Shabaana A.

Issue&Volume: 2023-04-03

Abstract: Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize TFH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.

DOI: 10.1038/s41590-023-01476-3