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*
Department of Cell Biology and Histology, University of Amsterdam, Amsterdam Medical Center, Amsterdam, The Netherlands;
Pfizer Global Research and Development, Fresnes, France;
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; and
Laboratory for Immunological Research, Schering-Plough, Dardilly, France
Immature dendritic cells (DC) reside in peripheral tissues, where
they pick up and process incoming pathogens via scavenger receptors or
FcR such as Fc
R and Fc
R. At mucosal surfaces, IgA is the main Ig
to protect the body from incoming pathogens. In addition, DC are
present in high numbers at these sites. We detected expression of
Fc
R (CD89) on the CD14+ population of CD34+
progenitor-derived DC and on monocyte-derived DC (MoDC). However, CD89
expression was strongly decreased upon differentiation from monocyte to
DC. We found only minimal binding of serum IgA to MoDC but strong
binding of secretory IgA (SIgA). The SIgA binding to MoDC could not be
blocked by anti-CD89 blocking Abs. DC efficiently internalized
SIgA, but not serum IgA, and uptake of SIgA could be blocked by
specific sugars or partially by Ab reactive with mannose receptor.
Importantly, binding and uptake of SIgA was not accompanied by signs of
DC maturation, such as increased expression of CD86 and CD83 or
induction of cytokine secretion. These data indicate that SIgA can
interact with DC not via CD89, but via carbohydrate-recognizing
receptors like mannose receptor and suggest that uptake of
SIgA-containing immune complexes by immature DC may be a mechanism to
modulate mucosal immune responses.
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