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Tango of B cells with T cells in the making of secretory antibodies to gut bacteria

Nature Reviews Gastroenterology & Hepatology volume 20, pages 120–128 (2023)Cite this article

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Abstract

Polymeric IgA and IgM are transported across the epithelial barrier from plasma cells in the lamina propria to exert a function in the gut lumen as secretory antibodies. Many secretory antibodies are reactive with the gut bacteria, and mounting evidence suggests that these antibodies are important for the host to control gut bacterial communities. However, we have incomplete knowledge of how bacteria-reactive secretory antibodies are formed. Antibodies from gut plasma cells often show bacterial cross-species reactivity, putting the degree of specificity behind anti-bacterial antibody responses into question. Such cross-species reactive antibodies frequently recognize non-genome-encoded membrane glycan structures. On the other hand, the T cell epitopes are peptides encoded in the bacterial genomes, thereby allowing a higher degree of predictable specificity on the T cell side of anti-bacterial immune responses. In this Perspective, we argue that the production of bacteria-reactive secretory antibodies is mainly controlled by the antigen specificity of T cells, which provide help to B cells. To be able to harness this system (for instance, for manipulation with vaccines), we need to obtain insight into the bacterial epitopes recognized by T cells in addition to characterizing the reactivity of the antibodies.

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Fig. 1: Surface structures of bacteria.
Fig. 2: Inductive and effector immune sites in the gut.
Fig. 3: T cell-dependent activation of bacteria-reactive B cells.

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Acknowledgements

The authors’ research is funded by grants from Stiftelsen KG Jebsen (project SKGJ-MED-017), the University of Oslo World-leading research program on human immunology (WL-IMMUNOLOGY) and the South-Eastern Norway Regional Health Authority (projects 2016113, 2020027 and 2022071).

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  1. K.G. Jebsen Coeliac Disease Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    Ludvig M. Sollid & Rasmus Iversen

  2. Department of Immunology, Oslo University Hospital – Rikshospitalet, Oslo, Norway

    Ludvig M. Sollid & Rasmus Iversen

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Sollid, L.M., Iversen, R. Tango of B cells with T cells in the making of secretory antibodies to gut bacteria. Nat Rev Gastroenterol Hepatol 20, 120–128 (2023). https://doi.org/10.1038/s41575-022-00674-y

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