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

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files Selective IgA deficiency (IgAD) is the most common primary antibody deficiency in the western world with affected indivi...

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Bibliographic Details
Published in:Frontiers in Immunology
Main Authors: Lemarquis, Andri L, Einarsdottir, Helga K, Kristjansdottir, Rakel N, Jonsdottir, Ingileif, Ludviksson, Bjorn R
Other Authors: 1 Landspitali Univ Hosp, Dept Immunol, Reykjavik, Iceland Show more 2 Univ Iceland, Fac Med, Reykjavik, Iceland 3 deCODE Genet, Div Infect & Inflammatory Dis, Reykjavik, Iceland
Format: Article in Journal/Newspaper
Language:English
Published: Frontiers Media SA 2018
Subjects:
Sjálfsofnæmissjúkdómar
Ónæmiskerfi
Mótefni
NAF12
AAI12
IgA Deficiency
Autoimmune Diseases
Iceland
Online Access:http://hdl.handle.net/2336/620590
https://doi.org/10.3389/fimmu.2018.00909
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Summary:To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files 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 results demonstrate a defect of the TLR9 responses in IgAD that leads to B cell dysregulation and decreased IgA production. Icelandic Research Fund University hospital of Iceland research fund

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