Hagiwara S
Department of International Medicine, Kobe University School of Medicine.
Kobe J Med Sci. 1996 Feb;42(1):43-59.
Recently we isolated a novel gene, VpreB-3 gene from the cDNA library of a pre-B cell clone. This gene is selectively expressed in pre-B and bone marrow-derived B cell lines. Its products are associated with the immunoglobulin heavy (IgH) chain in pre-B cell line. In the present study, to address the role of VpreB-3 on B cell development, transgenic mice carrying the VpreB-3 gene under the control of the IgH enhancer and SV40 promoter were produced. The transgenic mice expressed the VpreB-3 gene in bone marrow and spleen at a high level compared with control mice. In the thymus, the expression of the transgene was also detected, although its level was low. Flow cytometry analysis revealed that the frequency of CD45R+ and mu+ B cells were reduced in the bone marrow of 2 of the 11 transgenic mice and also reduced in the spleen of 1 of the transgenic mice. Furthermore, the results of a stromal cell-dependent B cell culture assay suggested that early B cell development, the differentiation from CD45R- B progenitor cells to CD45R+ pro-B cells, was delayed in the bone marrow cultures of 3 of the 5 transgenic mice compared with the control mice. These results suggested that VpreB-3 products may play some role in early B cell development at the stage of CD45R- B progenitor cells before the expression of surface mu chains.
最近，我们从一个前B细胞克隆的cDNA文库中分离出一个新基因——VpreB-3基因。该基因在人前B细胞和骨髓来源的B细胞系中选择性表达。其产物在前B细胞系中与免疫球蛋白重链（IgH）相关。在本研究中，为了探讨VpreB-3在B细胞发育中的作用，我们构建了在IgH增强子和SV40启动子控制下携带VpreB-3基因的转基因小鼠。与对照小鼠相比，转基因小鼠在骨髓和脾脏中高水平表达VpreB-3基因。在胸腺中也检测到转基因的表达，尽管其水平较低。流式细胞术分析显示，11只转基因小鼠中有2只的骨髓中CD45R+和μ+ B细胞的频率降低，1只转基因小鼠的脾脏中也降低。此外，基质细胞依赖性B细胞培养试验结果表明，与对照小鼠相比，5只转基因小鼠中有3只的骨髓培养物中，早期B细胞发育，即从CD45R- B祖细胞向CD45R+前B细胞的分化延迟。这些结果表明，VpreB-3产物可能在表面μ链表达之前的CD45R- B祖细胞阶段的早期B细胞发育中发挥一定作用。
