The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut.
In the Peyer's patches (PPs), germinal centers (GCs) are chronically induced by bacteria and are the major sites for generation of gut immunoglobulin A (IgA) immune responses. Whether follicular dendritic cells (FDCs) within the GCs directly contribute to the IgA production in PPs is unknown. We showed here that direct stimulation of FDCs by bacterial products and retinoic acid synergistically enhanced the expression of the chemokine CXCL13, the survival factor BAFF, and molecules that facilitate the secretion and activation of the cytokine TGF-beta1. A reduced production of these molecules by PP FDCs associated with deficiencies in the Toll-like receptor pathway or vitamin A resulted in decreased numbers of GC B cells and defective generation of IgA(+) B cells within PP GCs. Our data indicate that PP FDCs are conditioned by environmental stimuli to express key factors for B cell migration, survival, and preferential generation of IgA in gut.
Suzuki
Keiichiro
K
Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama 1-7-22, Tsurumi, Yokohama, 230-0045, Japan.
Maruya
Mikako
M
Kawamoto
Shimpei
S
Sitnik
Katarzyna
K
Kitamura
Hiroshi
H
Agace
William W
WW
Fagarasan
Sidonia
S
D000818:Animals; D000917:Antibody Formation; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000235:genetics / Q000378:metabolism*; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000473:pathology; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000235:genetics; D007155:Immunologic Factors / Q000494:pharmacology*; D051379:Mice; D010581:Peyer's Patches / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014802:Vitamin A Deficiency
D053264:B-Cell Activating Factor; D054382:Chemokine CXCL13; D007070:Immunoglobulin A; D007155:Immunologic Factors; C505720:Tnfsf13b protein, mouse; D051193:Toll-Like Receptors; D053773:Transforming Growth Factor beta1