Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine

We have revealed that 100-200 clusters, filled with closely packed lymphocytes, can be found throughout the length of the anti-mesenteric 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(+)IgM(low)IgD(high)CD5(-)M-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-beta (-/-), and Ig mu -chain mutant (mum(-/-)) 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-beta (-/-), and mum(-/-) 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-7R alpha (-/-) PPnull mice. Neither ILF nor PP are detectable in lymphotoxin alpha (-/-) and aly/aly mice that retain well-developed cryptopatches (CP) and thymus-independent subsets of intraepithelial T cells, whereas ELF, PP, CP, and thymus-independent subsets of intraepithelial T cells disappear from common cytokine receptor gamma -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.