title: Distinct developmental requirements for isolated lymphoid follicle formation in the small and large intestine: RANKL is essential only in the small intestine.
abstract: Cryptopatches (CPs) and isolated lymphoid follicles (ILFs) are organized intestinal lymphoid tissues that develop postnatally in mice and include stromal cells expressing the receptor activator of nuclear factor kappa-B ligand (RANKL). We investigated how stromal RANKL influences the development and differentiation of CPs and ILFs by analyzing the development of these lymphoid structures in knockout mice lacking RANKL. We found that RANKL(-/-) mice had a fourfold reduction in the overall density of CPs in the small intestine compared to control mice, with the largest decrease in the proximal small intestine. No B cells were present in CPs from the small intestine of RANKL(-/-) mice and ILF formation was completely blocked. In sharp contrast, colonic ILFs containing B cells were present in RANKL(-/-) mice. Stromal cells within CPs in the small intestine of RANKL(-/-) mice did not express CXCL13 (originally called B lymphocyte chemoattractant) and often lacked other normally expressed stromal cell antigens, whereas colonic lymphoid aggregates in RANKL(-/-) mice retained stromal CXCL13 expression. The CXCL13-dependent maturation of precursor CPs into ILFs is differentially regulated in the small intestine and colon, with an absolute requirement for RANKL only in the small intestine.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Knoop
authors.forename: Betsy R
authors.initials: BR
authors.lastname: Butler
authors.forename: Nachiket
authors.initials: N
authors.lastname: Kumar
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Newberry
authors.forename: Ifor R
authors.initials: IR
authors.lastname: Williams
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000473:pathology; D039521:CD11c Antigen / Q000378:metabolism; D002452:Cell Count; D054382:Chemokine CXCL13 / Q000378:metabolism; D006801:Humans; D007420:Intestine, Large / Q000196:embryology* / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000196:embryology* / Q000276:immunology* / Q000473:pathology; D008221:Lymphoid Tissue / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D053259:Lymphotoxin beta Receptor / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D038081:Organogenesis; D053245:RANK Ligand / Q000172:deficiency / Q000378:metabolism*; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology
chemical_list: D000941:Antigens; D039521:CD11c Antigen; D054382:Chemokine CXCL13; D053259:Lymphotoxin beta Receptor; D053245:RANK Ligand