Display of native antigen on cDC1 that have spatial access to both T and B cells underlies efficient humoral vaccination

Yu Kato, Thiago M. Steiner, Hae-Young Park, Rohan O. Hitchcock, Ali Zaid, Jyh Liang Hor, Sapna Devi, Gayle M. Davey, David Vremec, Kirsteen M. Tullett, Peck S. Tan, Fatma Ahmet, Scott N. Mueller, Sylvie Alonso, David M. Tarlinton, Hidde L. Ploegh, Tsuneyasu Kaisho, Lynette Beattie, Jonathan H. Manton, Daniel Fernandez-RuizKen Shortman, Mireille H. Lahoud, William R. Heath, Irina Caminschi

Research output: Contribution to journalArticleResearchpeer-review

10 Citations (Scopus)

Abstract

Follicular dendritic cells and macrophages have been strongly implicated in presentation of native Ag to B cells. This property has also occasionally been attributed to conventional dendritic cells (cDC) but is generally masked by their essential role in T cell priming. cDC can be divided into two main subsets, cDC1 and cDC2, with recent evidence suggesting that cDC2 are primarily responsible for initiating B cell and T follicular helper responses. This conclusion is, however, at odds with evidence that targeting Ag to Clec9A (DNGR1), expressed by cDC1, induces strong humoral responses. In this study, we reveal that murine cDC1 interact extensively with B cells at the border of B cell follicles and, when Ag is targeted to Clec9A, can display native Ag for B cell activation. This leads to efficient induction of humoral immunity. Our findings indicate that surface display of native Ag on cDC with access to both T and B cells is key to efficient humoral vaccination.

Original languageEnglish
Pages (from-to)1842-1856
Number of pages15
JournalJournal of Immunology
Volume205
Issue number7
DOIs
Publication statusPublished - 1 Oct 2020

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