Abstract

Class‐switching of B cells to IgA can be induced via both T‐cell‐dependent and T‐cell‐independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub‐optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T‐cell‐independent factors ‐promoting cell survival, class switching and immunoglobulin secretion‐ BAFF, APRIL, IL‐10 and retinoic acid can boost IgA production in the context of viral or bacterial infection. To this end total and naive peripheral blood B cells were stimulated with these factors for 6 days in the presence or absence of TLR7/8 agonist R848 (mimicking viral infection) or TLR9 agonist CpG‐ODN (mimicking bacterial infection). We show that BAFF significantly augments IgA2 production in TLR7/8 stimulated mature, but not naïve B cells. In addition, BAFF augments IL‐10 production and viability in TLR7/8 and TLR9 stimulated mature B cells. These data warrant further investigation of its role in immune regulation both in the periphery and mucosal tissues in early life or during disease.

Highlights

  • In early life, at the time the immune system develops, exposure to environmental pathogens, such as viruses and bacteria can lead to severe illness

  • BAFF and Retinoic acid (RA) significantly enhanced the viability induced by CpG-ODN, while BAFF augmented the increased viability induced by R848

  • After 6 days of culture the percentages of Transmembrane activator and CAML interactor · T cell independent (TI) (TACI) and IL-10R remained the same, in cells exposed to BAFF, a clear reduction in percentage of BAFF-R+ B cells was observed (Supporting Information Fig. 1B)

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Summary

Introduction

At the time the immune system develops, exposure to environmental pathogens, such as viruses and bacteria can lead to severe illness. The outcome of an immune response is partly dependent on the molecules in the immediate environment of cells; the niche. Proper discrimination must take place between pathogenic and commensal bacteria as well as between food ingredients, toxic substances or viral particles. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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