ArticleGastroenterology2011
IgA-producing plasma cells originate from germinal centers that are induced by B-cell receptor engagement in humans.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 76 citations in OpenAlex.
- Identification of marginal zone B cells in head and neck cancer with immunomodulatory characteristics.Journal of advanced research · 2026Article
- The role of mucosal immune dysregulation in the pathogenesis of immunoglobulin A nephropathy.Frontiers in immunology · 2026Review
- Capsaicin attenuates high-fat diet-induced impairment of B-cell immunity.SAGE open medicine · 2026Article
- Biomarker expression level changes within rectal gut-associated lymphoid tissues in spinal cord-injured rats.ImmunoHorizons · 2025Article
- Molecular and spatial analysis of tertiary lymphoid structures in Sjogren's syndrome.Nature communications · 2025Article
- All roads lead to IgA: Mapping the many pathways of IgA induction in the gut.Immunological reviews · 2024Review
- Role of cellular effectors in the induction and maintenance of IgA responses leading to protective immunity against enteric bacterial pathogens.Frontiers in immunology · 2024Review
- Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation.Immunity · 2023Article
- Intrinsic B cell TLR-BCR linked coengagement induces class-switched, hypermutated, neutralizing antibody responses in absence of T cells.Science advances · 2023Article
- Human intestinal B cells in inflammatory diseases.Nature reviews. Gastroenterology & hepatology · 2023Review
- Altered Immunoglobulin Repertoire and Decreased IgA Somatic Hypermutation in the Gut during Chronic HIV-1 Infection.Journal of virology · 2022Article
- Roles of Secretory Immunoglobulin A in Host-Microbiota Interactions in the Gut Ecosystem.Frontiers in microbiology · 2022Review
- The immune landscape of IgA induction in the gut.Seminars in immunopathology · 2021Review
- Know your enemy or find your friend?-Induction of IgA at mucosal surfaces.Immunological reviews · 2021Review
- Human gut-associated lymphoid tissues (GALT); diversity, structure, and function.Mucosal immunology · 2021Review
- High microbiota reactivity of adult human intestinal IgA requires somatic mutations.The Journal of experimental medicine · 2020Article
- IgA and the intestinal microbiota: the importance of being specific.Mucosal immunology · 2020Review
- Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue.Nature communications · 2018Article
- The regulation of gut mucosal IgA B-cell responses: recent developments.Mucosal immunology · 2017Review
- c-Rel is dispensable for the differentiation and functional maturation of M cells in the follicle-associated epithelium.Immunobiology · 2017Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsIgA contributes to homeostatic balance between host and intestinal microbiota. Mechanisms that initiate the IgA response are unclear and likely to differ between humans and animal models. We used multiple experimental approaches to investigate the origin of human intestinal plasma cells that produce IgA in the gastrointestinal tract.
methodsComplexity of IgA-producing plasma cell populations in human gastrointestinal mucosa and bone marrow and the specific response to oral cholera vaccine were compared by analysis of immunoglobulin genes. Flow cytometry, gene expression analysis, and immunohistochemistry were used to analyze signaling pathways induced by B-cell receptor engagement in human gut-associated lymphoid tissue (GALT) and involvement of innate immunity in B-cell activation in GALT compared with nonintestinal sites.
resultsHuman intestinal IgA-producing plasma cells appeared to be of germinal center origin; there was no evidence for the population complexity that accompanies multiple pathways of derivation observed in bone marrow. In germinal center B cells of human GALT, Btk and Erk are phosphorylated, CD22 is down-regulated, Lyn is translocated to the cell membrane, and Fos and Jun are up-regulated; these features indicate B-cell receptor ligation during germinal center evolution. No differences in innate activation of B cells were observed in GALT, compared with peripheral immune compartments.
conclusionsIgA-producing plasma cells appear to be derived from GALT germinal centers in humans. B-cell receptor engagement promotes formation of germinal centers of GALT, with no more evidence for innate immune receptor activation in the mucosa than nonintestinal immune compartments. Germinal centers in GALT should be targets of mucosal vaccinations because they are the source of human intestinal IgA response.
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Registered trials
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