Isolated Lymphoid Follicles are Dynamic Reservoirs for the Induction of Intestinal IgA

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.

Immunological Status of Isolated Lymphoid Follicles After Intestinal Transplantation

“…The output of proper function of follicular structures (inductive site) is IgA-secreting plasma cells in the LP of the gut mucosa, the effector site (15,17). Recently, the critical contribution of ILFs to luminal IgA production has been highlighted in mice (35) and in humans (36).…”

“…Mature ILFs contain a germinal center (GC) with mainly follicular B-lymphocytes (12), CD4 þ follicular helper T cells (T FH ) (13) and follicular dendritic cells (14). These small lymphoid structures seated all over the small bowel are highly dynamic serving as an important inductive site for IgA synthesis confronting changes in the microbiota (15,16). ILF hyperplasia and uncontrolled growth of commensals were shown in an activation-induced cytidine deaminase (AICDA) null mice, where class switch recombination and somatic hypermutation (SHM) are inhibited (17), whereas reduced number of ILFs were detected in antibiotic-treated or in germ-free mice (18,19).…”

Mucosal B Cell Differentiation and Regulation

“…PPs invariably host GCs (Macpherson et al, 2008), but whereas GCs within cPs have been described, they seem to be much less prevalent than in PPs Dohi et al, 1999Dohi et al, , 2001. Approximately 100-200 ILFs are present in each mouse small intestine, but only a small fraction of these are mature ILFs (mILFs) with GCs (Knoop and Newberry, 2012;Lorenz et al, 2003;Pabst et al, 2005). The B cell follicles of MLNs also occasionally contain GCs ).…”

“…Although not strictly a part of the GALT, the MLNs may also be involved in the generation of gut IgA responses, a function that is still incompletely investigated. follicles (ILFs) or solitary intestinal lymphoid tissues (Baptista et al, 2013;Knoop and Newberry, 2012). In addition, the appendix also contains abundant GALT (Spencer et al, 1985).…”

Mucosal Dendritic Cells

“…ILFs develop from rudimentary structures called cryptopatches (CP) that are collections of lymphoid-tissue inducer and lymphoid-tissue organizer cells present at birth. ILFs and CPs with or without DCs are collectively termed solitary isolated lymphoid tissue (see Knoop and Newberry, 2012). On bacterial colonization of germ-free mice, DCs are recruited to CPs and produce CXCL13 that attracts B cells to form an ILF.…”