The intestinal lumen contains an abundance of bacteria, viruses and fungi alongside ingested material that shape the chronically active intestinal immune system from early life to maintain the integrity of the gut epithelial barrier. In health, the response is intricately balanced to provide active protection against pathogen invasion whilst tolerating food and avoiding inflammation. B cells are central to achieving this protection. Their activation and maturation generates the body’s largest plasma cell population that secretes IgA, and the niches they provide support systemic immune cell specialization. For example, the gut supports the development and maturation of a splenic B cell subset — the marginal zone B cells. In addition, cells such as the T follicular helper cells, which are enriched in many autoinflammatory diseases, are intrinsically associated with the germinal centre microenvironment that is more abundant in the gut than in any other tissue in health. In this Review, we discuss intestinal B cells and their role when a loss of homeostasis results in intestinal and systemic inflammatory diseases.
Gut B cell responses are initiated in organized gut-associated lymphoid tissues (GALT).
Antibody-secreting plasma cells and their immediate precursors generated in GALT disseminate widely to diffusely populate the extensive lamina propria.
Although memory B cells expressing IgG in GALT are not uncommon in health, IgG-secreting intestinal plasma cells are.
Gut IgG plasma cells are major contributors to intestinal inflammation in inflammatory bowel disease.
The microbiota shapes many aspects of gut B cell responses, from determining the specificity of IgA responses to driving the functionality of regulatory B cells.
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Spencer, J., Bemark, M. Human intestinal B cells in inflammatory diseases. Nat Rev Gastroenterol Hepatol 20, 254–265 (2023). https://doi.org/10.1038/s41575-023-00755-6