B cells maintain the homeostasis of splenic marginal zone antigen-presenting cells to promote the antiviral CD8+ T-cell response

Natural killer and CD8<sup>+</sup> T cells are critical in the elimination of blood-borne viruses such as cytomegalovirus (CMV); however, the role of B cells in this process is less clear. Here, using a murine CMV (MCMV) infection model, we demonstrated that B-cell-deficient mice mounted a weaker primary virus-specific CD8<sup>+</sup> T-cell response than their wild-type counterparts did, which was associated with increased viral transcription. Notably, we found that the contribution of B cells to the CD8<sup>+</sup> T-cell-mediated antiviral response was not associated with their ability to generate antibodies but with their ability to sustain Langerin<sup>+</sup> type 1 conventional dendritic cells (cDC1s), a dendritic cell (DC) subset known for being involved in viral and bacterial clearance in the marginal zone of the spleen. Furthermore, we found that the presence of Langerin<sup>+</sup> cDC1s is dependent on B cells expressing lymphotoxin (LTβ) to maintain CD169<sup>+</sup> marginal metallophilic macrophages (MMMs). We further discovered, via ligand‒receptor interaction analyses, that the communication between MMMs and Langerin<sup>+</sup> cDC1s was mediated via the VCAM1-ITGA4/ITGB1 interaction. Thus, our data reveal that B cells regulate the development of MMMs in the spleen via LTβ expression and consequently sustain Langerin<sup>+</sup> cDC1 homeostasis for effective initiation of an antiviral CD8<sup>+</sup> T-cell response. Overall, our study offers a new perspective on how B cells maintain the homeostasis of antigen-presenting cells in the splenic marginal zone and thus indirectly affect the virus-specific CD8<sup>+</sup> T-cell response, which could be extended to other infectious and autoimmune diseases as well as tumors.

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Journal
Cellular and Molecular Immunology
Published
2026-02-24
DOI
https://doi.org/10.1038/s41423-026-01392-0
Primary Topic
Immunotherapy and Immune Responses
Type
article
Field-Weighted Citation Impact
0.00

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article

B cells maintain the homeostasis of splenic marginal zone antigen-presenting cells to promote the antiviral CD8+ T-cell response

A. Waisman, Xinyuan Liu, Lukas Bunse, David Alejandro Bejarano et al.
Cellular and Molecular Immunology
Immunotherapy and Immune Responses
article

B cells maintain the homeostasis of splenic marginal zone antigen-presenting cells to promote the antiviral CD8+ T-cell response

A. Waisman, Xinyuan Liu, Lukas Bunse, David Alejandro Bejarano, K. S. Lang, Ronald A. Backer, Ramon Arens, B. Clausen, Niels A. W. Lemmermann, Nadine Hövelmeyer, H. Probst, Lisa Johann, Filiz Demircik, Tobias Bopp, Esther von Stebut, Michaela Blanfeld, M. V. Antipova, Joke M. M. den Haan, Anna Ebering, Andreas Schlitzer, Abdelrahman Elwy, David C. Uhlfelder, B. Yiran Su, Katlynn Carter, Elisa Blickberndt, Yao Chen, Jennifer L. Gommerman, Matthias Klein
article en

Abstract

Natural killer and CD8<sup>+</sup> T cells are critical in the elimination of blood-borne viruses such as cytomegalovirus (CMV); however, the role of B cells in this process is less clear. Here, using a murine CMV (MCMV) infection model, we demonstrated that B-cell-deficient mice mounted a weaker primary virus-specific CD8<sup>+</sup> T-cell response than their wild-type counterparts did, which was associated with increased viral transcription. Notably, we found that the contribution of B cells to the CD8<sup>+</sup> T-cell-mediated antiviral response was not associated with their ability to generate antibodies but with their ability to sustain Langerin<sup>+</sup> type 1 conventional dendritic cells (cDC1s), a dendritic cell (DC) subset known for being involved in viral and bacterial clearance in the marginal zone of the spleen. Furthermore, we found that the presence of Langerin<sup>+</sup> cDC1s is dependent on B cells expressing lymphotoxin (LTβ) to maintain CD169<sup>+</sup> marginal metallophilic macrophages (MMMs). We further discovered, via ligand‒receptor interaction analyses, that the communication between MMMs and Langerin<sup>+</sup> cDC1s was mediated via the VCAM1-ITGA4/ITGB1 interaction. Thus, our data reveal that B cells regulate the development of MMMs in the spleen via LTβ expression and consequently sustain Langerin<sup>+</sup> cDC1 homeostasis for effective initiation of an antiviral CD8<sup>+</sup> T-cell response. Overall, our study offers a new perspective on how B cells maintain the homeostasis of antigen-presenting cells in the splenic marginal zone and thus indirectly affect the virus-specific CD8<sup>+</sup> T-cell response, which could be extended to other infectious and autoimmune diseases as well as tumors.

Cellular and Molecular Immunology
University of Bonn (DE), German Cancer Research Center (DE), University of Cologne (DE), Shanghai Jiao Tong University (CN), University of Toronto (CA), Johannes Gutenberg University Mainz (DE), Heidelberg University (DE), Leiden University Medical Center (NL), University Hospital Heidelberg (DE), University Medical Center of the Johannes Gutenberg University Mainz (DE), Bernstein Center for Computational Neuroscience Heidelberg-Mannheim (DE), Amsterdam University Medical Centers (NL), University Medical Centre Mannheim (DE), University of Duisburg-Essen (DE), Vrije Universiteit Amsterdam (NL)
Deutsche Forschungsgemeinschaft, National Natural Science Foundation of China, Rheinische Friedrich-Wilhelms-Universität Bonn, Canadian Institutes of Health Research
Openalex Percentile: Top 44%
Immunotherapy and Immune Responses
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