biostudies-literatureNarr KSwiss National Science FoundationEuropean Research CouncilSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschunge2108157118https://www.ebi.ac.uk/biostudies/studies/S-EPMC8694065biostudies-literatureUnknown118(46)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 foProceedings of the National Academy of Sciences of the United States of AmericaVaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection.PMC8694065323630323630_151472310962310030151472173010310030_173010310030_173132173132Ertuna YIDimitrova MWagner ICornille KAbreu Mota TMerkler DMarx AFLohning MKunzli MKing CGPinschewer DDMartin KGeier FFallet BBestmann LNarr KKreutzfeldt MSchreiner DBrunner TMfalseVaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection.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 fo2021-01-01T00:00:00Z2021 Nov2025-04-04T07:46:36.552Z2025-04-04T07:46:36.552ZS-EPMC86940653477281110.1073/pnas.2108157118