Open AccessBILL-Cadherin/Cadherin-17 Contributes to the Survival of Memory B Cells
Author(s) -
Shuichi Funakoshi,
Takeyuki Shimizu,
Osamu Numata,
Manabu Ato,
Fritz Melchers,
Kouhei Ohnishi
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0117566
Subject(s) - biology , cadherin , antigen , stromal cell , bone marrow , antibody , spleen , microbiology and biotechnology , immunology , cell , cancer research , genetics
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.