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B cell-derived type I interferon sustains T cell functionality upon strong TCR stimulation during chronic infection.

Immunity

Authors: Catarina Gago da Graça, Yuxi Cao, Sining Li, Anna F Lindemann, Leonie Heyden, Sharanya K M Wijesinghe, Annika Poch, Minh-Hanh T Nguyen, Nhat T Huynh-Anh, Elena Daum, Danielle Chen, Carlson Tsui, Erandi Rupasinghe, Michael P Gantier, Axel Roers, Robert Thimme, Maike Hofmann, Sammy Bedoui, Zeinab Abdullah, Jan Schröder, Axel Kallies, Yannick O Alexandre, Daniel T Utzschneider

B cells are highly abundant lymphocytes and central players in humoral immunity. Although T cells are well known to support humoral responses, how B cells influence T cell responses is less understood. Here, we show that B cells are critical for CD8 T cell responses to chronic, but not acute, viral infections. In the absence of B cells, T cells responding to chronic infection exhibited severely impaired effector differentiation. This dependency on B cell help was dictated by high antigen loads and strong T cell receptor (TCR) stimulation. Loss of either B cells or interferon-I (IFN-I) signaling led to severe functional deficits in exhausted T cells, implicating B cells as key producers of IFN-I. The IFN-I-dependent T cell response to strong TCR stimulation is mediated, in part, by the transcription factor IRF1. Therefore, during chronic infection, we uncover an important role for B cell-derived IFN-I in modulating T cell responses to strong TCR stimulation.

Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.

PMID: 42392074

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