Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization

Bemark, Mats; Hazanov, Helena; Strömberg, Anneli; Komban, Rathan Joy; Holmqvist, Joel; Köster, Sofia; Mattsson, Johan; Sikora, Per; Mehr, Ramit; Lycke, Nils

doi:10.1038/ncomms12698

Cited by 73 publications

(65 citation statements)

References 47 publications

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“…By comparison, IgA + plasma cells actively secrete antibody without receptor engagement, thus providing a constitutive humoral shield against systemic bacterial invasion. Notably, both pools of IgA-secreting cells consist mainly of long-lived cells (Bemark et al, 2016)(our unpublished results), and therefore provide a mechanism for the continuous production of serum antibodies with anti-microbial activity. These ideas therefore build on recent evidence that serum IgG antibodies specific for intestinal microbes form a barrier of protection against systemic invasion by commensal bacteria (Koch et al, 2016; Zeng et al, 2016).…”

Section: Discussionmentioning

confidence: 90%

Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis

Wilmore

Gaudette

Atria

et al. 2018

Cell Host & Microbe

182

191

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Serum immunoglobulin A (IgA) antibodies are readily detected in mice and people, but the mechanisms underlying the induction of serum IgA and its role in host protection remain uncertain. We report that select commensal bacteria induce several facets of systemic IgA-mediated immunity. Exposing conventional mice to a unique but natural microflora that included several members of the Proteobacteria phylum led to T cell-dependent increases in serum IgA levels and the induction of large numbers of IgA-secreting plasma cells in the bone marrow. The resulting serum IgA bound to a restricted collection of bacterial taxa, and antigen-specific serum IgA antibodies were readily induced after intestinal colonization with the commensal bacterium Helicobacter muridarum. Finally, movement to a Proteobacteria-rich microbiota led to serum IgA-mediated resistance to polymicrobial sepsis. We conclude that commensal microbes overtly influence the serum IgA repertoire, resulting in constitutive protection against bacterial sepsis.

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Section: Discussionmentioning

confidence: 90%

Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis

Wilmore

Gaudette

Atria

et al. 2018

Cell Host & Microbe

182

191

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“…Whereas, serum antibodies act after pathogen invasion, SIgA is localized on the external surface of epithelial cells in direct contact with commensal and pathogenic microorganisms. In the gut, SIgA regulates the diversity of the microbiota (2,3) and modulates immune activation by enteric commensals and food antigens (4). Moreover, SIgA, by controlling intestinal homeostasis, plays a role in the prevention of bacteria-driven inflammatory, autoimmune, and neoplastic B cell pathology (5).…”

Section: Introductionmentioning

confidence: 99%

Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis

et al. 2020

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Background: B-1a B cells and gut secretory IgA (SIgA) are absent in asplenic mice. Human immunoglobulin M (IgM) memory B cells, which are functionally equivalent to mouse B-1a B cells, are reduced after splenectomy. Objective: To demonstrate whether IgM memory B cells are necessary for generating IgA-secreting plasma cells in the human gut. Methods: We studied intestinal SIgA in two disorders sharing the IgM memory B cell defect, namely asplenia, and common variable immune deficiency (CVID). Results: Splenectomy was associated with reduced circulating IgM memory B cells and disappearance of intestinal IgA-secreting plasma cells. CVID patients with reduced circulating IgM memory B cells had a reduced frequency of gut IgA + plasma cells and a disrupted film of SIgA on epithelial cells. Toll-like receptor 9 (TLR9) and transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) induced IgM memory B cell differentiation into IgA + plasma cells in vitro. In the human gut, TACI-expressing IgM memory B cells were localized under the epithelial cell layer where the TACI ligand a proliferation inducing ligand (APRIL) was extremely abundant. Conclusions: Circulating IgM memory B cell depletion was associated with a defect of intestinal IgA-secreting plasma cells in asplenia and CVID. The observation that IgM memory B cells have a distinctive role in mucosal protection suggests the existence of a functional gut-spleen axis.

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“…10,11 Mucosal priming has been shown to induce LLPCs secreting IgA 1 antigen-specific antibodies in murine BM. 12 We thus examined whether rotavirus-specific LLPCs could be detected in human BM.…”

Section: Resultsmentioning

confidence: 99%

Long-lived plasma cells in human bone marrow can be either CD19+ or CD19–

et al. 2017

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Limited clonal relatedness between gut IgA plasma cells and memory B cells after oral immunization

Cited by 73 publications

References 47 publications

Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis

Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis

Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis

Long-lived plasma cells in human bone marrow can be either CD19+ or CD19–

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