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
TITLE=Lack of Gut Secretory Immunoglobulin A in Memory B-Cell Dysfunction-Associated Disorders: A Possible Gut-Spleen Axis
JOURNAL=Frontiers in Immunology
VOLUME=10
YEAR=2020
URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02937
DOI=10.3389/fimmu.2019.02937
ISSN=1664-3224
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.