Wenjuan Zheng, Yu Tang, Mengwei Cheng, Cui Ma, X. Fei, W. Shi
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引用次数: 0
摘要
外周血b淋巴细胞和骨髓b淋巴细胞(BM)对淋巴抑制剂或免疫抑制剂表现出不同的反应。我们探讨了b淋巴细胞在外周和骨髓间室分布失调的存在及其潜在机制。MRL/lpr小鼠和SLE患者外周血(PB)中CXC趋化因子受体4+ B (CXCR4+ B)细胞百分比降低,BM中CXCR4+ B细胞百分比升高。来自MRL/lpr小鼠和SLE患者的BM成骨细胞(OBs)产生的CXC趋化因子配体12 (CXCL12)高于C57BL/6小鼠或健康受试者。MRL/lpr衍生OBs对b淋巴细胞的趋化能力强于对照OBs, MRL/lpr小鼠骨膜带内OBs共定位的b淋巴细胞较多。CXCR4+ B细胞百分比与血清免疫球蛋白G浓度呈负相关,BM CXCL12水平与系统性红斑狼疮疾病活动性指数评分和抗双链DNA滴度呈正相关,与血清补体3浓度呈负相关。总之,我们的研究结果表明,在SLE患者和MRL/lpr小鼠中,b淋巴细胞在基底细胞和外周腔室之间的分布发生了转移,而ob中CXCL12的上调可能有助于b淋巴细胞向ob的趋化迁移和锚定增强。
Dysregulated CXCL12 Expression in Osteoblasts Promotes B-lymphocytes Preferentially Homing to the Bone Marrow in MRL/lpr Mice
Peripheral circulating B-lymphocytes and B-lymphocytes in the bone marrow (BM) show different responses to lymphotoxic or immunosuppressive agents. We explored the existence of a dysregulated distribution of B-lymphocytes between peripheral and BM compartments and the underlying mechanisms. The percentage of CXC chemokine receptor 4+ B (CXCR4+ B) cells was decreased in the peripheral blood (PB) and increased in the BM of MRL/lpr mice and SLE patients. CXC chemokine ligand 12 (CXCL12) production by BM osteoblasts (OBs) derived from MRL/lpr mice and SLE patients was higher than that obtained with C57BL/6 mice or healthy subjects. MRL/lpr-derived OBs demonstrated stronger chemotactic ability toward B-lymphocytes than control OBs, and more B-lymphocytes colocalized with OBs within the periosteal zone in MRL/lpr mice. Moreover, the CXCR4+ B cell percentages were negatively correlated with the serum immunoglobulin G concentration, and the BM CXCL12 levels were positively correlated with the systemic lupus erythematosus disease activity index score and anti-double stranded DNA titer and negatively correlated with the serum complement 3 concentration. In conclusion, our results indicate a shifted distribution of B-lymphocytes between the BM and peripheral compartments in SLE patients and MRL/lpr mice and that the upregulation of CXCL12 in OBs likely contributes to enhanced chemotactic migration and anchorage of B-lymphocytes to OBs.