Journal Article

DKFZ-2026-00435

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png B cells maintain the homeostasis of splenic marginal zone antigen-presenting cells to promote the antiviral CD8+ T-cell response.

Liu, X. ; Demircik, F. ; Antipova, M. ; Stylianakis, E. ; Klein, M. ; Bejarano, D. ; Elwy, A. ; Ebering, A. ; Blanfeld, M. ; Carter, K. ; Johann, L. ; Uhlfelder, D. C. ; Blickberndt, E. ; Chen, Y. ; Probst, H. C. ; Hövelmeyer, N. ; Bopp, T. ; Arens, R. ; Bunse, L.DKFZ* ; den Haan, J. M. M. ; Gommerman, J. L. ; von Stebut, E. ; Clausen, B. E. ; Schlitzer, A. ; Lang, K. S. ; Su, B. ; Backer, R. A. ; Lemmermann, N. A. ; Waisman, A.

2026
Nature Publ. Group London [u.a.]

Abstract: Natural killer and CD8+ 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+ 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+ T-cell-mediated antiviral response was not associated with their ability to generate antibodies but with their ability to sustain Langerin+ 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+ cDC1s is dependent on B cells expressing lymphotoxin (LTβ) to maintain CD169+ marginal metallophilic macrophages (MMMs). We further discovered, via ligand‒receptor interaction analyses, that the communication between MMMs and Langerin+ 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+ cDC1 homeostasis for effective initiation of an antiviral CD8+ 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+ T-cell response, which could be extended to other infectious and autoimmune diseases as well as tumors.

Keyword(s): B cells ; anti-viral CD8+ T-cell response ; splenic marginal zone antigen-presenting cells

Note: #DKTKZFB26# / 2026 Apr;23(4):383-399

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Contributing Institute(s):

1. KKE Neuroimmunologie und Hirntumorimmunologie (D170)
2. DKTK HD zentral (HD01)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2026

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Essential Science Indicators ; IF >= 20 ; JCR ; Nationallizenz ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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