IgA-Producing B Cells in the Intestine
An overview of intestinal IgA-B cell development is shown below.
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Overview of IgA-B Cell Pathway
IgA is the dominant class of immuoglobulins in the intestine and is key to host immunity. In the lamina propria, which lies between the intestinal epithelium and muscle wall, follicular dendritic cells (FDC) produce the chemokine CXCL13/BLC/BCA-1 to attract CXCR5-expressing B cells, T follicular helper cells (Tfh), and T follicular regulatory cells (Tfr). Immature B cells are exposed to antigen by direct contact with FDC. B cells also interact with Tfh and Tfr cells through co-stimulatory or inhibitory proteins in the B7/CD28 and SLAM families. These cell clusters constitute the immune follicles characteristic of gut-associated lymphoid tissue (GALT) and are known as Peyer’s patches. In a Peyer’s patch, the combination of cell-cell contacts and cytokines produced by FDC, Tfh, and Tfr cells induce the B cell to undergo immunoglobulin class-switching to IgA and become a rapidly-dividing plasmablast. Additional FDC-derived factors induce the plasmablast to enter the circulation, home to the intestinal mucosa (via newly upregulated Integrin alpha 4 beta 7, CCR9, and CCR10), and develop into a plasma cell. Plasma cells secrete large amounts of IgA which binds to the receptor pIgR on enterocytes for transport across the epithelium. Secretory IgA (sIgA) in the intestinal lumen is trapped in the mucous layer where it functions as a critical component of host immunity to intestinal pathogens as well as immune tolerance to commensal microbiota.
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