title: BILL-cadherin/cadherin-17 contributes to the survival of memory B cells.
abstract: Memory B cells (MBCs) and long-lived plasma cells (LLPCs) are responsible for immunological "memory", which can last for many years. The long-term survival niche for LLPCs in the bone marrow is well characterized; however, the corresponding niche for MBCs is unclear. BILL-cadherin/cadherin-17 (CDH17) is the only member of the cadherin superfamily that is expressed on mouse B lymphocytes in a spatiotemporally regulated manner. Here, we show that half of all MBCs regain expression of CDH17 during the later stage of development. The maintenance of high affinity antigen-specific serum antibodies was impaired in CDH17(-/-) mice and the number of antigen-specific MBCs was reduced as compared to wild-type mice (WT). Also, specific responses to secondary antigens were ablated in CDH17(-/-) mice, whereas primary antibody responses were the same as those in WT mice. Cell cycle analysis revealed a decline in the proliferation of CDH17(-) MBCs as compared to CDH17(+) MBCs. In addition, we identified a subpopulation of splenic stromal cells, MAdCAM-1(+) blood endothelial cells (BEC), which was CDH17(+). Taken together, these results suggest that CDH17 plays a role in the long-term survival of MBCs, presumably via an "MBC niche" comprising, at least in part, BEC in the spleen.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan; Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Funakoshi
authors.affiliation: Department of Immunology, Kochi Medical School, Kochi University, Kochi, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Faculty of Life and Environmental Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Numata
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ato
authors.affiliation: Research Group of Lymphocyte Development, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Fritz
authors.initials: F
authors.lastname: Melchers
authors.affiliation: Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ohnishi
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D000918:Antibody Specificity / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015820:Cadherins / Q000235:genetics / Q000276:immunology*; D002453:Cell Cycle / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D015820:Cadherins; C490585:Cdh17 protein, mouse