IgA Function in Relation to the Intestinal Microbiota

Abstract

IgA is the dominant immunoglobulin isotype produced in mammals, largely secreted across the intestinal mucosal surface. Although induction of IgA has been a hallmark feature of microbiota colonization following colonization in germ-free animals, until recently appreciation of the function of IgA in host-microbial mutualism has depended mainly on indirect evidence of alterations in microbiota composition or penetration of microbes in the absence of somatic mutations in IgA (or compensatory IgM). Highly parallel sequencing techniques that enable high-resolution analysis of either microbial consortia or IgA sequence diversity are now giving us new perspectives on selective targeting of microbial taxa and the trajectory of IgA diversification according to induction mechanisms, between different individuals and over time. The prospects are to link the range of diversified IgA clonotypes to specific antigenic functions in modulating the microbiota composition, position and metabolism to ensure host mutualism.

The continuing story of T‐cell independent antibodies

“…66 Interactions between the intestinal microbiota and immune cells including dendritic cells within the lamina propria of the small intestine (siLP) readily engender the genesis of IgA-producing plasma cells. 67,68 Such cells are mainly produced in Peyer's patches and mesenteric lymph nodes, but then relocate to the siLP where they secrete dimeric IgA molecules that are actively transported into the intestinal lumen where they bind to a host of commensal bacteria. 69 Notably, the bulk of the IgA-producing plasma cell pool in the siLP consists of long-lived cells 70 (our unpublished data).…”

Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin

“…SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport dIgA and pIgM through the mucosal epithelial cells 7–10 . SIgA forms a critical first line of defense against pathogens at the mucosal surface, and also likely plays an important role in regulating the homeostasis of microbiota 11,12 . SIgA in breast milk is important for protecting the newborn babies until their own immune systems have developed.…”

Transcriptional factor ATF3 protects against colitis by regulating follicular helper T cells in Peyer’s patches

“…activating transcription factor 3 | follicular helper T cell | Peyer's patches | intestinal mucosal immunity | colitis D efects in the gut mucosal immune system play an important role in the pathogenesis of inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis (UC). Gut microbiota promote the development of gut-associated lymphoid tissues (GALTs), which are responsible for the production of secretory IgA (sIgA) in the gut (1,2). sIgA in lumen functions to maintain the indigenous members of microbiota and prevent the colonization of harmful microbes (3,4).…”