BILL-cadherin/cadherin-17 contributes to the survival of memory B cells.

BILL-cadherin/cadherin-17 contributes to the survival of memory B cells.
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DOI:
10.1371/journal.pone.0117566
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Ohnishi K
Ohnishi K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Funakoshi S;Shimizu T;Numata O;Ato M;Melchers F;Ohnishi K

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记忆B细胞(MBC)和长寿浆细胞(LLPC)负责免疫“记忆”,可持续多年。LLPC在骨髓中的长期生存生态位已得到很好的表征;然而,MBC的相应生态位尚不清楚。BILL-钙粘蛋白/钙粘蛋白-17(CDH 17)是钙粘蛋白超家族中唯一以时空调节的方式在小鼠B淋巴细胞上表达的成员。在这里,我们发现,一半的MBC在发育后期重新表达CDH 17。与野生型小鼠(WT)相比,CDH 17-/-小鼠中高亲和力抗原特异性血清抗体的维持受损,抗原特异性MBC的数量减少。此外,在CDH 17-/-小鼠中消除了对第二抗原的特异性应答,而第一抗体应答与WT小鼠中的那些相同。细胞周期分析显示,与CDH 17 + MBCs相比,CDH 17- MBCs的增殖下降。此外,我们鉴定了脾基质细胞的亚群,MAdCAM-1+血内皮细胞(BEC),其为CDH 17+。总之,这些结果表明,CDH 17在MBC的长期存活中起作用,推测是通过至少部分地包含脾脏中的BEC的“MBC生态位”。
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.
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