Cargando…
Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis
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 Ig...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960143/ https://www.ncbi.nlm.nih.gov/pubmed/31969880 http://dx.doi.org/10.3389/fimmu.2019.02937 |
_version_ | 1783487728023764992 |
---|---|
author | Carsetti, Rita Di Sabatino, Antonio Rosado, Maria Manuela Cascioli, Simona Piano Mortari, Eva Milito, Cinzia Grimsholm, Ola Aranburu, Alaitz Giorda, Ezio Tinozzi, Francesco Paolo Pulvirenti, Federica Donato, Giuseppe Morini, Francesco Bagolan, Pietro Corazza, Gino Roberto Quinti, Isabella |
author_facet | Carsetti, Rita Di Sabatino, Antonio Rosado, Maria Manuela Cascioli, Simona Piano Mortari, Eva Milito, Cinzia Grimsholm, Ola Aranburu, Alaitz Giorda, Ezio Tinozzi, Francesco Paolo Pulvirenti, Federica Donato, Giuseppe Morini, Francesco Bagolan, Pietro Corazza, Gino Roberto Quinti, Isabella |
author_sort | Carsetti, Rita |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6960143 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69601432020-01-22 Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis Carsetti, Rita Di Sabatino, Antonio Rosado, Maria Manuela Cascioli, Simona Piano Mortari, Eva Milito, Cinzia Grimsholm, Ola Aranburu, Alaitz Giorda, Ezio Tinozzi, Francesco Paolo Pulvirenti, Federica Donato, Giuseppe Morini, Francesco Bagolan, Pietro Corazza, Gino Roberto Quinti, Isabella Front Immunol Immunology 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. Frontiers Media S.A. 2020-01-08 /pmc/articles/PMC6960143/ /pubmed/31969880 http://dx.doi.org/10.3389/fimmu.2019.02937 Text en Copyright © 2020 Carsetti, Di Sabatino, Rosado, Cascioli, Piano Mortari, Milito, Grimsholm, Aranburu, Giorda, Tinozzi, Pulvirenti, Donato, Morini, Bagolan, Corazza and Quinti. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Carsetti, Rita Di Sabatino, Antonio Rosado, Maria Manuela Cascioli, Simona Piano Mortari, Eva Milito, Cinzia Grimsholm, Ola Aranburu, Alaitz Giorda, Ezio Tinozzi, Francesco Paolo Pulvirenti, Federica Donato, Giuseppe Morini, Francesco Bagolan, Pietro Corazza, Gino Roberto Quinti, Isabella Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis |
title | Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis |
title_full | Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis |
title_fullStr | Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis |
title_full_unstemmed | Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis |
title_short | Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis |
title_sort | lack of gut secretory immunoglobulin a in memory b-cell dysfunction-associated disorders: a possible gut-spleen axis |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960143/ https://www.ncbi.nlm.nih.gov/pubmed/31969880 http://dx.doi.org/10.3389/fimmu.2019.02937 |
work_keys_str_mv | AT carsettirita lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT disabatinoantonio lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT rosadomariamanuela lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT casciolisimona lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT pianomortarieva lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT militocinzia lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT grimsholmola lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT aranburualaitz lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT giordaezio lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT tinozzifrancescopaolo lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT pulvirentifederica lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT donatogiuseppe lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT morinifrancesco lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT bagolanpietro lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT corazzaginoroberto lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis AT quintiisabella lackofgutsecretoryimmunoglobulinainmemorybcelldysfunctionassociateddisordersapossiblegutspleenaxis |