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)/ B细胞前生长刺激因子（PBSF））及其主要生理受体CXCR4对B细胞发育和造血细胞在骨髓中的定植至关重要。在本研究中，我们进一步分析了CXCL12在造血器官间和造血器官内造血细胞动员中的作用。(1)造血干细胞（Hematopoietic stem cells, hsc）具有移动性，在个体发育过程中发生了一系列的造血定植事件。我们通过长期再生实验和细胞归巢实验证明，CXCL12在造血干细胞和髓系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并在骨髓内发育，对CXCL12的依赖性最早出现在pre-pro-B细胞。我们发现表达cxcl12的细胞是一小部分基质细胞，具有几个过程，分布在骨髓中，并位于与表达白细胞介素(IL)-7的细胞有一定距离的地方。多能造血祖细胞附着在表达cxcl12的细胞突起上，前-前- b细胞附着在其细胞体上。需要IL-7的成熟前b细胞已经离开并靠近表达IL-7的细胞。成熟前b细胞不与表达il -7的细胞接触。此外，终末期B细胞、浆细胞再次产生表达cxcl12的细胞。因此，我们已经确定了B淋巴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运动，并表明CXCL12维持了生态位中的前体。综上所述，CXCL12可能在造血细胞与骨髓中特定细胞龛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.