The Sensing of Environmental Stimuli by Follicular Dendritic Cells Promotes Immunoglobulin A Generation in the Gut

• Published in: Immunity (Cambridge, Mass.) Vol. 33; no. 1; pp. 71 - 83
• Main Authors: Suzuki, Keiichiro, Maruya, Mikako, Kawamoto, Shimpei, Sitnik, Katarzyna, Kitamura, Hiroshi, Agace, William W., Fagarasan, Sidonia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23-07-2010; Elsevier Limited
• Subjects: Animals; Antibody Formation; B-Cell Activating Factor - genetics; B-Cell Activating Factor - metabolism; Basic Medicine; Cell Survival - drug effects; CELLIMMUNO; Cells, Cultured; Chemokine CXCL13 - genetics; Chemokine CXCL13 - metabolism; Chemokines; Dendritic Cells, Follicular - immunology; Dendritic Cells, Follicular - metabolism; Dendritic Cells, Follicular - pathology; Gene expression; Gene Expression Profiling; Germinal Center - pathology; Immune system; Immunity, Mucosal; Immunoglobulin A - biosynthesis; Immunoglobulin A - genetics; Immunologi inom det medicinska området; Immunologic Factors - pharmacology; Immunology in the medical area; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Metabolites; Mice; Peyer's Patches - pathology; Signal Transduction; Software; Toll-Like Receptors - metabolism; Transforming Growth Factor beta1 - metabolism; Vitamin A Deficiency; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2010.07.003

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-β1. 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.
► FDCs from Peyer's patches have unique molecular signatures ► PP FDC transcripts reflect exposure to bacterial components and retinoic acid ► TLR and RAR signaling increases expression of BAFF, CXCL13, and TGF-β1 activators ► FDCs are critical for IgA synthesis in the germinal center of Peyer's patches