美国阿拉巴马大学伯明翰分校André Ballesteros-Tato团队近期取得重要工作进展，他们研究发现，Tfh细胞产生的干扰素γ是CXCR3⁺前记忆B细胞分化和随后的肺驻留记忆B细胞反应所必需的。相关研究成果2023年9月11日在线发表于《免疫》杂志上。

据介绍，肺驻留记忆B细胞（肺BRM）在再次感染后分化为浆细胞，提供增强的肺部保护。

研究人员探讨了流感感染时肺BRM分化的决定因素。动力学分析显示，流感核蛋白（NP）特异性BRM在感染后早期优先分化，需要T滤泡辅助细胞（Tfh）的帮助。BRM分化在时间上与Tfh细胞产生瞬时干扰素（IFN）-γ相一致。Tfh细胞中IFN-γ的缺失阻止了肺BRM的分化，并损害了对异亚型感染的保护。生发中心（GC）B细胞表达转录因子T-bet需要IFN-γ，这促进了作为纵隔淋巴结中肺BRM和CXCR3⁺记忆B细胞的前体的CXCR3⁺ GC B细胞亚群的分化。GC B细胞中缺乏IFN-γ信号传导或T-bet会阻止CXCR3⁺记忆前体的发育，并阻碍CXCR3⁺记忆B细胞的分化和随后的肺BRM反应。

因此，Tfh细胞来源的IFN-γ对肺BRM的发展和肺免疫至关重要，对靶向BRM的疫苗接种策略有意义。

附：英文原文

Title: Interferon-γ production by Tfh cells is required for CXCR3+ pre-memory B cell differentiation and subsequent lung-resident memory B cell responses

Author: Nicole M. Arroyo-Díaz, Holly Bachus, Amber Papillion, Troy D. Randall, Jobaida Akther, Alexander F. Rosenberg, Beatriz León, André Ballesteros-Tato

Issue&Volume:

Abstract: Lung-resident memory B cells (lung-BRMs) differentiate into plasma cells after reinfection,providing enhanced pulmonary protection. Here, we investigated the determinants oflung-BRM differentiation upon influenza infection. Kinetic analyses revealed thatinfluenza nucleoprotein (NP)-specific BRMs preferentially differentiated early afterinfection and required T follicular helper (Tfh) cell help. BRM differentiation temporallycoincided with transient interferon (IFN)-γ production by Tfh cells. Depletion ofIFN-γ in Tfh cells prevented lung-BRM differentiation and impaired protection againstheterosubtypic infection. IFN-γ was required for expression of the transcription factorT-bet by germinal center (GC) B cells, which promoted differentiation of a CXCR3+ GC B cell subset that were precursors of lung-BRMs and CXCR3+ memory B cells in the mediastinal lymph node. Absence of IFN-γ signaling or T-betin GC B cells prevented CXCR3+ pre-memory precursor development and hampered CXCR3+ memory B cell differentiation and subsequent lung-BRM responses. Thus, Tfh-cell-derivedIFN-γ is critical for lung-BRM development and pulmonary immunity, with implicationsfor vaccination strategies targeting BRMs.

DOI: 10.1016/j.immuni.2023.08.015

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00371-0