PDF(Pubmed)
Abstract：
Lung-resident memory B cells (lung-BRMs) differentiate into plasma cells after reinfection, providing enhanced pulmonary protection. Here, we investigated the determinants of lung-BRM differentiation upon influenza infection. Kinetic analyses revealed that influenza nucleoprotein (NP)-specific BRMs preferentially differentiated early after infection and required T follicular helper (Tfh) cell help. BRM differentiation temporally coincided with transient interferon (IFN)-γ production by Tfh cells. Depletion of IFN-γ in Tfh cells prevented lung-BRM differentiation and impaired protection against heterosubtypic infection. IFN-γ was required for expression of the transcription factor T-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-bet in GC B cells prevented CXCR3+ pre-memory precursor development and hampered CXCR3+ memory B cell differentiation and subsequent lung-BRM responses. Thus, Tfh-cell-derived IFN-γ is critical for lung-BRM development and pulmonary immunity, with implications for vaccination strategies targeting BRMs.
摘要：
肺驻留记忆B细胞（肺BRM）在再感染后分化为浆细胞，提供增强的肺保护。这里,我们调查了流感感染后肺-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（Tfh）细胞帮助。BRM分化与Tfh细胞的瞬时干扰素（IFN）-γ产生时间一致。Tfh细胞中IFN-γ的消耗阻止了肺BRM分化和对异型感染的保护作用。生发中心（GC）B细胞表达转录因子T-bet需要IFN-γ，促进纵隔淋巴结中作为肺BRM和CXCR3记忆B细胞前体的CXCR3GCB细胞亚群的分化。GCB细胞中IFN-γ信号传导或T-bet的缺乏阻止了CXCR3+前记忆前体的发育并阻碍了CXCR3+记忆B细胞分化和随后的肺-BRM应答。因此，Tfh细胞来源的IFN-γ对于肺BRM发育和肺免疫至关重要，对针对BRM的疫苗接种策略有影响。
