Abstract
IgA is one of the most important molecules in the regulation of intestinal homeostasis. Peyer’s patches have been traditionally recognized as sites for the induction of intestinal IgA responses, however more recent studies demonstrate that isolated lymphoid follicles (ILFs) can perform this function as well. ILF development is dynamic, changing in response to the luminal microbial burden, suggesting that ILFs play an important role providing an expandable reservoir of compensatory IgA inductive sites. However, in situations of immune dysfunction, ILFs can over-develop in response to uncontrollable enteric flora, resulting in ILF hyperplasia. The ability of ILFs to expand and respond to help control the enteric flora makes this dynamic reservoir an important arm of IgA inductive sites in intestinal immunity.
Highlights
IgA is the most abundantly produced antibody, representing 70% of antibody production (Macpherson and Uhr, 2004; Macpherson et al, 2008)
Activation-induced cytidine deaminase (AID), necessary for both class-switch recombination (CSR) and somatic hypermutation (SHM), is present in Peyer’s patches (PPs) B cells. It is thought PPs utilize mostly T cell dependent routes for IgA production as germinal center formation in PPs is dependent on both CD40–CD40L signaling from T cells (Bergqvist et al, 2006) and the presence of T cells (Tsuji et al, 2008)
While evidence to support that a large population of IgA producing plasma cells resides in the isolated lymphoid follicles (ILFs) in the setting of CCR10 sufficiency is lacking and the migration and fate of ILF generated IgA+ plasmablasts is largely unknown, it is clear in this model that ILF development is increased in response to the commensals, and that IgA is induced within ILFs to control the enteric flora
Summary
IgA is the most abundantly produced antibody, representing 70% of antibody production (Macpherson and Uhr, 2004; Macpherson et al, 2008). Within the mucosal lymphoid tissues of the intestinal tract, made up of Peyer’s patches (PPs), ILFs, and Colonic Patches, TGFβ1 is crucial for IgA production and expressed by several cell types promoting the majority of gut B cells to differentiate into IgA producing plasma cells (Coffman et al, 1989). Activation-induced cytidine deaminase (AID), necessary for both CSR and somatic hypermutation (SHM), is present in PP B cells It is thought PPs utilize mostly T cell dependent routes for IgA production as germinal center formation in PPs is dependent on both CD40–CD40L signaling from T cells (Bergqvist et al, 2006) and the presence of T cells (Tsuji et al, 2008). In contrast to PPs, which remain fully developed throughout life, SILT are a spectrum of lymphoid www.frontiersin.org
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