Arakawa-Hoyt J, Dao M A, Thiemann F, Hao Q L, Ertl D C, Weinberg K I, Crooks G M, Nolta J A
Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital, Los Angeles, CA, USA.
Bone Marrow Transplant. 1999 Dec;24(11):1167-76. doi: 10.1038/sj.bmt.1702048.
The lack of human B lymphocyte development in beige/nude/XID (bnx) mice is in sharp contrast to the robust development observed in another immune deficient strain, the NOD/SCID mouse. The ability to generate human B lymphocytes in the NOD/SCID, but not bnx mouse has been hypothesized to be caused by differences in the microenvironments or systemic cytokine concentrations. In the current studies we report that the differences in development can be primarily attributed to the source of the progenitors transplanted into the mice. The prior studies in bnx mice used cultured pediatric or adult bone marrow (BM) as the source of the CD34+ cells, whereas the NOD/SCID studies have predominantly used fresh or cultured umbilical cord blood (UCB). We have analyzed BM and UCB for the number of human CD34+/CD38- cells capable of in vitro B lymphocyte development, and have found a lower frequency of B lymphocyte generation in BM. The individual B lymphocyte clones that developed from bone marrow produced 100-fold fewer cells than the UCB-derived clones. In agreement with the in vitro studies, human B lymphocytes developed in bnx mice from both CD34+ and CD34+/CD38- cells isolated from human umbilical cord blood, but not from equivalent numbers of CD34+ and CD34+/CD38- progenitors from bone marrow. Therefore, the lower generative capacity, and frequency of B lymphocyte precursors in human marrow may be responsible for the previous results that showed a lack of B lymphocyte development in bnx mice.
米色/裸鼠/XID（bnx）小鼠缺乏人类B淋巴细胞发育，这与另一种免疫缺陷品系NOD/SCID小鼠中观察到的强劲发育形成鲜明对比。据推测，NOD/SCID小鼠而非bnx小鼠能够产生人类B淋巴细胞是由微环境或全身细胞因子浓度的差异所致。在当前研究中，我们报告发育差异主要可归因于移植到小鼠体内的祖细胞来源。先前对bnx小鼠的研究使用培养的儿科或成人骨髓（BM）作为CD34+细胞的来源，而NOD/SCID研究主要使用新鲜或培养的脐带血（UCB）。我们分析了BM和UCB中能够进行体外B淋巴细胞发育的人类CD34+/CD38-细胞数量，发现BM中B淋巴细胞生成频率较低。从骨髓发育而来的单个B淋巴细胞克隆产生的细胞比UCB来源的克隆少100倍。与体外研究一致，bnx小鼠中的人类B淋巴细胞由从人脐带血分离的CD34+和CD34+/CD38-细胞发育而来，但不是由等量的来自骨髓的CD34+和CD34+/CD38-祖细胞发育而来。因此，人类骨髓中较低的生成能力和B淋巴细胞前体频率可能是先前结果中显示bnx小鼠缺乏B淋巴细胞发育的原因。
