Ratliff Michelle L, Ward Julie M, Merrill Joan T, James Judith A, Webb Carol F
Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104;
Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104; Microbiology and Immunology Program, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104;
J Immunol. 2015 Feb 1;194(3):940-9. doi: 10.4049/jimmunol.1401941. Epub 2014 Dec 22.
Although hematopoietic stem/progenitor cells (HSPCs) are used for transplantation, characterization of the multiple subsets within this population in humans has lagged behind similar studies in mice. We found that expression of the DNA-binding protein, ARID3a, in mouse stem cells was important for normal development of hematopoietic lineages; however, progenitors expressing ARID3a in humans have not been defined. We previously showed increased numbers of ARID3a(+) B cells in nearly half of systemic lupus erythematosus (SLE) patients, and total numbers of ARID3a(+) B cells were associated with increased disease severity. Because expression of ARID3a in those SLE patients occurred throughout all B cell subsets, we hypothesized that ARID3a expression in patient HSPCs might also be increased relative to expression in healthy controls. Our data now show that ARID3a expression is not limited to any defined subset of HSPCs in either healthy controls or SLE patients. Numbers of ARID3a(+) HSPCs in SLE patients were increased over numbers of ARID3a(+) cells in healthy controls. Although all SLE-derived HSPCs exhibited poor colony formation in vitro compared with controls, SLE HSPCs with high numbers of ARID3a(+) cells yielded increased numbers of cells expressing the early progenitor marker, CD34. SLE HSPCs with high numbers of ARID3a(+) cells also more readily generated autoantibody-producing cells than HSPCs with lower levels of ARID3a in a humanized mouse model. These data reveal new functions for ARID3a in early hematopoiesis and suggest that knowledge regarding ARID3a levels in HSPCs could be informative for applications requiring transplantation of those cells.
尽管造血干/祖细胞（HSPCs）可用于移植，但人类该群体中多个亚群的特征描述落后于小鼠的类似研究。我们发现，DNA结合蛋白ARID3a在小鼠干细胞中的表达对造血谱系的正常发育很重要；然而，人类中表达ARID3a的祖细胞尚未明确。我们之前发现，近一半的系统性红斑狼疮（SLE）患者中ARID3a(+) B细胞数量增加，且ARID3a(+) B细胞总数与疾病严重程度增加相关。由于这些SLE患者中ARID3a的表达在所有B细胞亚群中均有发生，我们推测患者HSPCs中ARID3a的表达相对于健康对照可能也会增加。我们现在的数据表明，无论是健康对照还是SLE患者，ARID3a的表达都不限于HSPCs的任何特定亚群。SLE患者中ARID3a(+) HSPCs的数量高于健康对照中ARID3a(+)细胞的数量。尽管与对照相比，所有来源于SLE的HSPCs在体外均表现出较差的集落形成能力，但ARID3a(+)细胞数量较多的SLE HSPCs产生表达早期祖细胞标志物CD34的细胞数量增加。在人源化小鼠模型中，ARID3a(+)细胞数量较多的SLE HSPCs也比ARID3a水平较低的HSPCs更容易产生自身抗体产生细胞。这些数据揭示了ARID3a在早期造血中的新功能，并表明有关HSPCs中ARID3a水平的知识可能对需要移植这些细胞的应用具有参考价值。
