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.

Lack of gut secretory immunoglobulin A in memory B-cell dysfunction-associated disorders: a possible gut-spleen axis / Carsetti, R.; Di Sabatino, A.; Rosado, M. M.; Cascioli, S.; Piano Mortari, E.; Milito, C.; Grimsholm, O.; Aranburu, A.; Giorda, E.; Tinozzi, F. P.; Pulvirenti, F.; Donato, G.; Morini, F.; Bagolan, P.; Corazza, G. R.; Quinti, I.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 10:(2020). [10.3389/fimmu.2019.02937]

Lack of gut secretory immunoglobulin A in memory B-cell dysfunction-associated disorders: a possible gut-spleen axis

Cascioli S.;Piano Mortari E.;Milito C.;Morini F.;Quinti I.
2020

Abstract

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.
2020
common variable immune deficiency; gut mucosal immunology; plasma cell; splenectomy; transmembrane activator and calcium-modulator and cyclophilin ligand interactor
01 Pubblicazione su rivista::01a Articolo in rivista
Lack of gut secretory immunoglobulin A in memory B-cell dysfunction-associated disorders: a possible gut-spleen axis / Carsetti, R.; Di Sabatino, A.; Rosado, M. M.; Cascioli, S.; Piano Mortari, E.; Milito, C.; Grimsholm, O.; Aranburu, A.; Giorda, E.; Tinozzi, F. P.; Pulvirenti, F.; Donato, G.; Morini, F.; Bagolan, P.; Corazza, G. R.; Quinti, I.. - In: FRONTIERS IN IMMUNOLOGY. - ISSN 1664-3224. - 10:(2020). [10.3389/fimmu.2019.02937]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1360773
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