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Antigen targeting reveals splenic CD169+ macrophages as promoters of germinal
center B-cell responses
#MMPMID25487358
Veninga H
; Borg EG
; Vreeman K
; Taylor PR
; Kalay H
; van Kooyk Y
; Kraal G
; Martinez-Pomares L
; den Haan JM
Eur J Immunol
2015[Mar]; 45
(3
): 747-57
PMID25487358
show ga
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.
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