title: Antigen targeting reveals splenic CD169+ macrophages as promoters of germinal center B-cell responses.
abstract: Ag delivery to specific APCs is an attractive approach in developing strategies for vaccination. CD169(+) macrophages in the marginal zone of the spleen represent a suitable target for delivery of Ag because of their strategic location, which is optimal for the capture of blood-borne Ag and their close proximity to B cells and T cells in the white pulp. Here we show that Ag targeting to CD169(+) macrophages in mice resulted in strong, isotype-switched, high-affinity Ab production and the preferential induction and long-term persistence of Ag-specific GC B cells and follicular Th cells. In agreement with these observations, CD169(+) macrophages retained intact Ag, induced cognate activation of B cells, and increased expression of costimulatory molecules upon activation. In addition, macrophages were required for the production of cytokines that promote B-cell responses. Our results identify CD169(+) macrophages as promoters of high-affinity humoral immune responses and emphasize the value of CD169 as target for Ag delivery to improve vaccine responses.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Henrike
authors.initials: H
authors.lastname: Veninga
authors.forename: Ellen G F
authors.initials: EG
authors.lastname: Borg
authors.forename: Kyle
authors.initials: K
authors.lastname: Vreeman
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Hakan
authors.initials: H
authors.lastname: Kalay
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
authors.forename: Georg
authors.initials: G
authors.lastname: Kraal
authors.forename: Luisa
authors.initials: L
authors.lastname: Martinez-Pomares
authors.forename: Joke M M
authors.initials: JM
authors.lastname: den Haan
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
chemical_list: D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse
keywords: B-cell response; CD169; Germinal center; Macrophage; Spleen