Transitional B Cells and TLR9 Responses Are Defective in Selective IgA Deficiency

Frontiers in Immunology
Andri L LemarquisBjorn R Ludviksson

Abstract

Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected individuals suffering from an increased burden of autoimmunity, atopic diseases and infections. It has been shown that IgAD B cells can be induced with germinal center mimicking reactions to produce IgA. However, IgA is the most prevalent antibody in mucosal sites, where antigen-independent responses are important. Much interest has recently focused on the role of TLR9 in both naïve and mature B cell differentiation into IgA secreting plasma cells. Here, we analyze the phenotype and function of T and B cells in individuals with IgAD following IgA-inducing CpG-TLR9 stimulations. The IgAD individuals had significantly lower numbers of transitional B cells (CD19+CD24hiCD38hi) and class-switched memory B cells (CD20+CD27+IgD-) ex vivo. However, proportions of T cell populations ex vivo as well as in vitro induced T effector cells and T regulatory cells were comparable to healthy controls. After CpG stimulation, the transitional B cell defect was further enhanced, especially within its B regulatory subset expressing IL-10. Finally, CpG stimulation failed to induce IgA production in IgAD individuals. Collectively, our res...Continue Reading

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Citations

Jul 29, 2020·International Journal of Molecular Sciences·Ida Judyta MaleszaPiotr Eder
May 2, 2020·Clinical & Translational Immunology·Christina Grosserichter-WagenerMenno C van Zelm
Apr 3, 2019·Frontiers in Immunology·Andri L LemarquisBjorn R Ludviksson
Apr 16, 2019·Frontiers in Immunology·Annelot Breedveld, Marjolein van Egmond
Sep 25, 2021·Clinical and Experimental Immunology·Motoshi SonodaShouichi Ohga
May 16, 2019·International Archives of Allergy and Immunology·Yasser BagheriAsghar Aghamohammadi

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Methods Mentioned

BETA
flow cytometry
flow
enzyme-linked immunosorbent assay
PMA
ELISA

Software Mentioned

GraphPad Prism
Flow Jo Tree star

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