Unknown

Dataset Information

0

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


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.

SUBMITTER: Carsetti R 

PROVIDER: S-EPMC6960143 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

altmetric image

Publications


<b>Background:</b> 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. <b>Objective:</b> To demonstrate whether IgM memory B cells are necessary for generating IgA-secreting plasma cells in the human gut. <b>Methods:</b> We studied intestinal SIgA in two disorders sharing the IgM memory B cell defect, namely asplenia, and common variable immune d  ...[more]

Similar Datasets

| S-EPMC7438410 | biostudies-literature
| S-EPMC6199361 | biostudies-literature
| S-EPMC7012952 | biostudies-literature
| S-EPMC7685991 | biostudies-literature
| S-EPMC5233583 | biostudies-literature
| S-EPMC7707832 | biostudies-literature
| S-EPMC8021727 | biostudies-literature
| S-EPMC5610266 | biostudies-literature
| S-EPMC8085382 | biostudies-literature
| S-EPMC7912098 | biostudies-literature