Antibody responses initiated by Clec9A-bearing dendritic cells in normal and Batf3-/- mice

Irina Caminschi, David Vremec, Fatma Ahmet, Mireille H. Lahoud, Jose A. Villadangos, Kenneth M. Murphy, William R. Heath, Ken Shortman

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Injection of antigens coupled to antibodies against the dendritic cell (DC) surface molecule Clec9A has been shown to produce strongly enhanced antibody responses even without co-administration of adjuvants, via antigen presentation by DC on MHC class II and consequent production of follicular helper T cells. A series of mutant mice were tested to determine the DC subtypes responsible for this MHC II presentation of targeted antigen, compared to presentation of antigen on MHC I. A new clec9A null mouse was developed; these mice did not give enhanced antibody production, confirming the response was dependent on Clec9A-expressing DC. However targeting of antigen to Clec9A in batf3 null mice produced enhanced antibody responses despite the marked reduction in CD8+ DC, the major Clec9A-expressing DC subtype. This was shown to be dependent on efficient MHC II presentation by minor Clec9A-expressing DC subtypes in the environment of the Batf3-/- mice, namely early cells of the CD8 DC lineage and the plasmacytoid-related CD8+ DC subset, but not by plasmacytoid cells themselves. However in normal mice most MHC II presentation of the Clec9A-targeted antigen was by the major CD8+ DC population, the DC also responsible for presentation on MHC I.

Original languageEnglish
Pages (from-to)9-17
Number of pages9
JournalMolecular Immunology
Volume50
Issue number1-2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Keywords

  • Batf3
  • Dendritic cells
  • Targeting Clec9A

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    Caminschi, I., Vremec, D., Ahmet, F., Lahoud, M. H., Villadangos, J. A., Murphy, K. M., Heath, W. R., & Shortman, K. (2012). Antibody responses initiated by Clec9A-bearing dendritic cells in normal and Batf3-/- mice. Molecular Immunology, 50(1-2), 9-17. https://doi.org/10.1016/j.molimm.2011.11.008