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Science 314 (5802): 1157-1160

Copyright © 2006 by the American Association for the Advancement of Science

Generation of Gut-Homing IgA-Secreting B Cells by Intestinal Dendritic Cells

J. Rodrigo Mora,1*{dagger} 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{dagger}

Abstract: Normal intestinal mucosa contains abundant immunoglobulin A (IgA)–secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell–independent expression of IgA and gut-homing receptors on B cells. GALT-DC–derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC–derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and 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.

{dagger} 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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