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Display of Native Antigen on cDC1 That Have Spatial Access to Both T and B Cells Underlies Efficient Humoral Vaccination

Y. Kato,Thiago M. Steiner,Hae-Young Park,Rohan O. Hitchcock,Ali Zaid,J. Hor,Sapna Devi,G. Davey,D. Vremec,Kirsteen M. Tullett,P. Tan,Fatma Ahmet,Scott N. Mueller,S. Alonso,D. Tarlinton,H. Ploegh,T. Kaisho,Lynette Beattie,J. Manton,Daniel Fernandez-Ruiz,K. Shortman,M. Lahoud,W. Heath,I. Caminschi

Published 2020 in Journal of Immunology

ABSTRACT

Key Points Clec9A-targeted Ag induces humoral responses. cDC1 directly present native Ag to B cells for B cell activation. Clec9A maintains native Ag on the cDC1 surface but DEC205 does not. Visual 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.

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