Identification of Multiple Isolated Lymphoid Follicles on the Antimesenteric Wall of the Mouse Small Intestine

Abstract

We have revealed that 100–200 clusters, filled with closely packed lymphocytes, can be found throughout the length of the antimesenteric wall of the mouse small intestine. They are composed of a large B cell area, including a germinal center, and epithelia overlying the clusters contain M cells. A large fraction of B cells displays B220+CD19+CD23+IgMlowIgDhighCD5−Mac-1− phenotype, and the composition of IgA+ B cells is smaller but substantial. To our knowledge, these clusters are the first identification of isolated lymphoid follicles (ILF) in mouse small intestine. ILF can be first detected at 7 (BALB/c mice) and 25 (C57BL/6 mice) days after birth, and lymphoid clusters equivalent in terms of cellular mass to ILF are present in germfree, athymic nude, RAG-2−/−, TCR-β−/−, and Ig μ-chain mutant (μm−/−) mice, although c-kit+ cells outnumber B220+ cells in germfree and athymic nude mice, and most lymphoid residents are c-kit+B220− in RAG-2−/−, TCR-β−/−, and μm−/− mice. ILF develop normally in the progeny of transplacentally manipulated Peyer’s patch (PP)-deficient mice, and decreased numbers of conspicuously atrophied ILF are present in IL-7Rα−/− PPnull mice. Neither ILF nor PP are detectable in lymphotoxin α−/− and aly/aly mice that retain well-developed cryptopatches (CP) and thymus-independent subsets of intraepithelial T cells, whereas ILF, PP, CP, and thymus-independent subsets of intraepithelial T cells disappear from common cytokine receptor γ-chain mutant mice. These findings indicate that ILF, PP, and CP constitute three distinct organized gut-associated lymphoid tissues that reside in the lamina propria of the mouse small intestine.

Vaccination against encapsulated bacteria in humans: paradoxes

“…It could alternatively occur in isolated B lymphoid follicles along the gut, as has been described for other species (see below). A [40] [ 41] similar pre-activated stage has been described for NK T cells , and, similarly to them, pre-activation of marginal zone B cells could be [42] driven by self or bacterial commensal antigens. For both these cellular populations, NKT and marginal zone B cells which are intermediate between the innate and adaptive immune system, this pre-activated stage may explain why they react very rapidly upon challenge by external bacterial antigens .…”

Distinct Developmental Requirements for Isolated Lymphoid Follicle Formation in the Small and Large Intestine

“…6 -8 An ILF is a single B-cell follicle that develops a germinal center on maturation and can serve as an inductive site for IgA responses. 9,10 A single ILF fills up an entire villus and is covered by a follicleassociated epithelium (FAE) containing M cells, that is similar to the FAE of PPs. A normal adult mouse has approximately 100 to 200 ILFs in the small intestine and 50 in the colon.…”

“…A normal adult mouse has approximately 100 to 200 ILFs in the small intestine and 50 in the colon. 9 Recently, it has been suggested that CPs and ILFs are not distinct types of intestinal lymphoid tissue, but rather two extremes on a continuum of solitary intestinal lymphoid tissue (SILT). 11 Current evidence suggests that the number of SILT structures in the intestine is normally stable after postnatal development is completed.…”

Prenatal Blockage of Lymphotoxin β Receptor and TNF Receptor p55 Signaling Cascade Resulted in the Acceleration of Tissue Genesis for Isolated Lymphoid Follicles in the Large Intestine

“…A recent study revealed the existence of isolated lymphoid follicles (ILF) in the small intestine that resemble PP in terms of architecture and cellular composition (8). The fact that ILF possess germinal centers and an overlying follicle-associated epithelium (FAE) containing M cells suggests their possible role as mucosal inductive sites (8).…”

“…It had been believed that PP is the major inductive site for the initiation of Ag-specific IgA responses to a variety of exogenous Ag (3,4); however, we and others have demonstrated that PP contribute to, but are not essential for, the induction of Agspecific mucosal IgA responses (5)(6)(7). A recent study revealed the existence of isolated lymphoid follicles (ILF) in the small intestine that resemble PP in terms of architecture and cellular composition (8). The fact that ILF possess germinal centers and an overlying follicle-associated epithelium (FAE) containing M cells suggests their possible role as mucosal inductive sites (8).…”