학술논문
Vaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection
Document Type
research-article
Author
Narr, Kerstin; Ertuna, Yusuf I.; Fallet, Benedict; Cornille, Karen; Dimitrova, Mirela; Marx, Anna-Friederike; Martin, Katrin; Mota, Tiago Jose Abreu; Künzli, Marco; Schreiner, David; Brunner, Tobias M.; Kreutzfeldt, Mario; Wagner, Ingrid; Geier, Florian; Bestmann, Lukas; Löhning, Max; Merkler, Doron; King, Carolyn G.; Pinschewer, Daniel D.
Source
Proceedings of the National Academy of Sciences of the United States of America, 2021 Nov . 118(46), 1-12.
Subject
Language
English
ISSN
00278424
10916490
10916490
Abstract
Chronic viral infections subvert protective B cell immunity. An early type I interferon (IFN-I)–driven bias to short-lived plasmablast differentiation leads to clonal deletion, so-called “decimation,” of antiviral memory B cells. Therefore, prophylactic countermeasures against decimation remain an unmet need. We show that vaccination-induced CD4 T cells prevented the decimation of naïve and memory B cells in chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. Although these B cell responses were largely T independent when IFN-I was blocked, preexisting T help assured their sustainability under conditions of IFN-I–driven inflammation by instructing a germinal center B cell transcriptional program. Prevention of decimation depended on T cell–intrinsic Bcl6 and Tfh progeny formation. Antigen presentation by B cells, interactions with antigen-specific T helper cells, and costimulation by CD40 and ICOS were also required. Importantly, B cell–mediated virus control averted Th1-driven immunopathology in LCMV-challenged animals with preexisting CD4 T cell immunity. Our findings show that vaccination-induced Tfh cells represent a cornerstone of effective B cell immunity to chronic virus challenge, pointing the way toward more effective B cell–based vaccination against persistent viral diseases.