The Journal of Experimental Medicine
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Published online 26 January 2004 doi:10.1084/jem.20030996
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 3, 411-416
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Brief Definitive Report

 Chemokine Receptor CCR9 Contributes to the Localization of Plasma Cells to the Small Intestine

Oliver Pabst1, Lars Ohl1, Meike Wendland1, Marc-André Wurbel2, Elisabeth Kremmer3, Bernard Malissen2, and Reinhold Förster1

1 Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany
2 Centre d'Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Medicale-Centre National de la Recherche Scientifique-Université de la Méditerranée, Parc Scientifique de Luminy, 13288 Marseille Cedex 9, France
3 Institute of Molecular Immunology, GSF, 81377 München, Germany

Address correspondence to Reinhold Förster, Institute of Immunology, Hannover Medical School, Feodor-Lynen-Str. 21, 30625 Hannover, Germany. Phone: 49-511-5329721; Fax: 49-511-5329722; email: foerster.reinhold{at}mh-hannover.de

Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.

Key Words: gut • IgA • lamina propria • CCL25 • cell trafficking


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