Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells.
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.
Mora
J Rodrigo
JR
CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA. mora@cbr.med.harvard.edu
Iwata
Makoto
M
Eksteen
Bertus
B
Song
Si-Young
SY
Junt
Tobias
T
Senman
Balimkiz
B
Otipoby
Kevin L
KL
Yokota
Aya
A
Takeuchi
Hajime
H
Ricciardi-Castagnoli
Paola
P
Rajewsky
Klaus
K
Adams
David H
DH
von Andrian
Ulrich H
UH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D003713:Dendritic Cells / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D007422:Intestines / Q000166:cytology / Q000276:immunology*; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D014212:Tretinoin / Q000276:immunology; D014801:Vitamin A / Q000502:physiology; D014802:Vitamin A Deficiency / Q000276:immunology; D014815:Vitamins / Q000276:immunology
D007070:Immunoglobulin A; D015848:Interleukin-5; D015850:Interleukin-6; D011947:Receptors, Antigen, B-Cell; D014815:Vitamins; D014801:Vitamin A; D014212:Tretinoin