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Generation of Gut-Homing IgA-Secreting B Cells by Intestinal Dendritic Cells
J. Rodrigo Mora,1*
Makoto Iwata,2*
Bertus Eksteen,3*
Si-Young Song,2
Tobias Junt,1
Balimkiz Senman,1
Kevin L. Otipoby,1
Aya Yokota,2
Hajime Takeuchi,2
Paola Ricciardi-Castagnoli,4
Klaus Rajewsky,1
David H. Adams,3
Ulrich H. von Andrian1
Abstract:
Normal intestinal mucosa contains abundant immunoglobulin A(IgA)secreting cells, which are generated from B cellsin gut-associated lymphoid tissues (GALT). We show that dendriticcells (DC) from GALT induce T cellindependent expressionof IgA and gut-homing receptors on B cells. GALT-DCderivedretinoic acid (RA) alone conferred gut tropism but could notpromote IgA secretion. However, RA potently synergized withGALT-DCderived interleukin-6 (IL-6) or IL-5 to induceIgA secretion. Consequently, mice deficient in the RA precursorvitamin A lacked IgA-secreting cells in the small intestine.Thus, GALT-DC shape mucosal immunity by modulating B cell migrationand effector activity through synergistically acting mediators.
1 CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. 2 Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki-shi, Kagawa 769-2193, Japan. 3 MRC Centre for Immune Regulation, University of Birmingham, Birmingham B15 2TT, UK. 4 Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, Milan, Italy.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: uva{at}cbr.med.harvard.edu (U.H.V.A.); mora{at}cbr.med.harvard.edu (J.R.M.)
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In Science Signaling
EDITORS' CHOICE
Stephen Simpson (21 November 2006) Sci. STKE2006 (362), tw398.
[DOI: 10.1126/stke.3622006tw398] |Abstract »
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