Mechanisms by which chemokine CXCL12 functions in hematopoiesis and lymphopoiesis

CXC趋化因子配体(CXCL)12(基质细胞衍生因子(SDF-1)/前B细胞生长刺激因子(PBSF))及其主要的生理受体CXCR4对B细胞的发育和骨髓在造血细胞中的定植是必不可少的。在这项研究中，我们进一步分析了CXCL12在造血器官之间和内部动员造血细胞的作用。(1)造血干细胞(HSCs)在个体发育过程中具有移动性，并发生一系列的造血定植事件。通过长期再繁殖实验和细胞归巢实验，我们证明了CXCL12在造血干细胞和髓样细胞从外周循环归巢到骨髓中起关键作用。(2)B淋巴细胞由造血干细胞产生，在骨髓内发育，对CXCL12的依赖最早出现在前B细胞阶段。我们发现表达CXCL12的细胞是一小群基质细胞，有几个突起，散布在骨髓中，距离表达白细胞介素7的细胞有一定的距离。多能造血祖细胞附着在表达CXCL12的细胞的突起上，前前B细胞附着在它们的细胞体上。需要IL-7的成熟的Pro-B细胞已经离开，并与表达IL-7的细胞毗邻。成熟的前B细胞不与表达IL-7的细胞接触。此外，终末期的B细胞、浆细胞再播种CXCL12表达细胞。因此，我们已经确定了B淋巴细胞生成的阶段特异性生态位，证明了B淋巴细胞在发育过程中在骨髓内特定生态位之间的特征定位和移动，并表明CXCL12维持了该生态位中的前体。总之，CXCL12很可能在造血细胞与骨髓中特定细胞生态位的相互作用中发挥关键作用。

CXC chemokine ligand (CXCL)12 (stromal cell-derived factor (SDF-1)/pre-B-cell-growth-stimulating factor(PBSF)) and its primary physiologic receptor CXCR4 are essential for B cell development and colonization of bone marrow by hematopoietic cells during. In this study, we have analyzed further the roles of CXCL12 in mobilization of hematopoietic cells between and within hematopoietic organs. (1)Hematopoietic stem cells(HSCs) are mobile and sequence of hematopoietic colonization events occurs during ontogeny. We have shown that CXCL12 plays a critical role in homing of HSCs and myeloid cells to bone marrow from the peripheral circulation using a long-term repopulation assay and cell homing assay. (2)B lymphocytes are generated from HSCs and develop within bone marrow and dependency on CXCL12 appears at the earliest stages, pre-pro-B cells. We have found that CXCL12-expressing cells are a small population of stromal cells, had several processes, are scattered throughout bone marrow and located some distance from the cells expressing interleukin (IL)-7. Multipotent hematopoietic progenitors are attached to the processes of CXCL12-expressing cells and pre-pro-B cells adjoin their cell bodies. Maturer pro-B cells, which require IL-7, have moved away and adjoin the IL-7-expressing cells. Maturer pre-B cells are not in contact with IL-7-expressing cells. Furthermore, the end-stage B cells, plasma cells again seed CXCL12-expressing cells. Thus, we have identified stage-specific niches for B lymphopoiesis, demonstrated the B lymphocyte characteristic location and movement between specific niches within bone marrow during development and suggested that CXCL12 maintains the precursors in the niche. Together, CXCL12 is likely to play a critical role in the interaction of hematopoictic cells with the specific cellular niches in bone marrow.