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

Authors :
Rita Carsetti
Antonio Di Sabatino
Maria Manuela Rosado
Simona Cascioli
Eva Piano Mortari
Cinzia Milito
Ola Grimsholm
Alaitz Aranburu
Ezio Giorda
Francesco Paolo Tinozzi
Federica Pulvirenti
Giuseppe Donato
Francesco Morini
Pietro Bagolan
Gino Roberto Corazza
Isabella Quinti
Source :
Frontiers in Immunology, Vol 10 (2020)
Publication Year :
2020
Publisher :
Frontiers Media S.A., 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.

Details

Language :
English
ISSN :
16643224
Volume :
10
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.37f68843b63841d29b064d7051d291f3
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2019.02937