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.
Highlights
BILL-cadherin/cadherin-17 (CDH17) is a cell adhesion molecule that belongs to the cadherin superfamily, a large group of cell adhesion molecules with properties similar to those of integrins and selectins
To investigate the possible roles of CDH17 in late B cell responses, we first analyzed the expression of CDH17 by various splenic B cell populations in wildtype mice (WT) immunized with nitrophenylated chicken gammaglobulin (NP-CGG) and in KO mice
To further characterize the CDH17+ and CDH17- Memory B cells (MBCs), we examined the expression of chemokine/cytokine receptors and other adhesion molecules (CXCR3, CCR6, integrin-β2, integrin-αL, VE-cadherin, CD80, and CD273) (S1 Fig.)
Summary
BILL-cadherin/cadherin-17 (CDH17) is a cell adhesion molecule that belongs to the cadherin superfamily, a large group (more than 100 members) of cell adhesion molecules with properties similar to those of integrins and selectins. Cadherins are Ca2+-dependent adhesion molecules characterized by their unique extracellular domains, which primarily comprise multiple cadherin-repeats. Cadherins primarily mediate homotypic (cell to cell) adhesion; they play important roles in intercellular recognition during embryogenesis and morphogenesis [1, 2]. Cadherin-17 Contributes to the B Cell Memory [3, 4]. CDH17 requires Ca2+ for homotypic adhesion [3, 5]; heterotypic adhesion to E-cadherin has been reported [6]. CDH17 is expressed in the spleen, bone marrow, and intestine [3, 7], whereas in rats it is expressed in the liver [4]
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