Molecular mechanism for memory B cell dynamics and survival

趋化性趋化因子在B细胞向不同组织的选择性募集、建立B细胞稳态和免疫应答中起重要作用。在这里，我们报告CC趋化因子受体D6和CCR 1的差异表达MZ和记忆B细胞在脾脏和B1细胞在腹腔。与以前的观察结果一致，B细胞亚群上的D6与其配体发生物理相互作用，内化并靶向其细胞内降解，但它不引起MZ B细胞和B1细胞的活化，如增殖、终末分化。结果提示，D6对B细胞亚群的真正作用是清除MZ B细胞和B1细胞周围微环境中的CC趋化因子。另外，在寻找记忆B细胞特异性基因的过程中，我们已经鉴定了在记忆细胞和边缘区B细胞中高水平表达的基因3940。在B细胞淋巴瘤细胞系中过表达3940导致在促凋亡条件下细胞存活的延长，表明3940可能在记忆B细胞的存活中起一定作用。

Chemotactic chemokines play important role in the selective recruitment of B cells to different histological tissues, establishing B cell homeostasis and immune response. Here we report that CC chemokine receptor D6 and CCR1 is differentially expressed on MZ and memory B cells in the spleen and B1 cells in the peritoneal cavity. In agreement with previous observations, D6 on B cell subsets physically interact with its ligands, internalize, and target them intracellular degradation, whereasa it did not cause activation of MZ B cells and B1 cells, such as proliferation, terminal differentiation. The results suggest that the genuine function of D6 on B cell subsets is to eliminate CC chemokines from microenvironment surrounding MZ B cell and B1 cells. In addition, during the course of search for memory B cells' specific genes, we have identified the gene 3940 who express at high levels in memory cells and marginal zone B cells. Over expression of 3940 in B cell lymphoma cell lines resulted in the prolongation of cell survival under the pro-apoptoic conditions, suggesting that 3940 may play some role in survival of memory B cells.