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

Autor:	Arroyo-Díaz NM; Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA., Bachus H; Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA., Papillion A; Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA., Randall TD; Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA., Akther J; Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA., Rosenberg AF; Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, USA; Informatics Institute, The University of Alabama at Birmingham, Birmingham, AL, USA., León B; Department of Microbiology, The University of Alabama at Birmingham, Birmingham, AL, USA., Ballesteros-Tato A; Department of Medicine, Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: andreballesterostato@uabmc.edu.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2023 Oct 10; Vol. 56 (10), pp. 2358-2372.e5. Date of Electronic Publication: 2023 Sep 11.
DOI:	10.1016/j.immuni.2023.08.015
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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