Human intestinal B cells in inflammatory diseases

Intestinal B cell responses are crucial in maintaining gut homeostasis. This Review discusses the role of human intestinal B cells in health and intestinal disease and provides a comprehensive overview of their features. 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.