Sagara S, Sugaya K, Tokoro Y, Tanaka S, Takano H, Kodama H, Nakauchi H, Takahama Y
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.
J Immunol. 1997 Jan 15;158(2):666-76.
The present study has characterized T lymphoid progenitor cells that reside in mouse fetal liver. Day 14 fetal liver contains progenitor cells that can differentiate into mature T cells upon being transferred into the thymus by hanging drop cultures. Fractionation of fetal liver cells indicated that T progenitor cells were confined in TER119- CD45+ FcR(low) cells. To our surprise, B220+ rather than B220- fraction in TER119- CD45+ FcR(low) fetal liver cells exhibited efficient progenitor activity generating T cells. Progenitor activity by the B220+ fetal liver cells was restricted to T cells, B cells, and macrophages at frequency approximately 1/10, approximately 1/10, and approximately 1/20, respectively, of isolated B220+ cells. B220+ fetal liver cells did not contain detectable D-J rearrangement of TCR-beta gene and were c-kit+ IL-7R+ Thy-1- CD3- CD4(low) CD8- CD25- CD44+. B220+ fetal liver cells expressed mRNAs encoding TCR-beta, pT alpha, Ig alpha, and VpreB. Interestingly, TCR beta-chains were expressed by B220+ fetal liver cells in the VDJ-rearranged TCR-beta-transgenic mice, indicating that TCR-beta transcription and B220 expression are activated simultaneously by the transgenic B220+ fetal liver cells. These results indicate that B220 is expressed by fetal liver lymphoid progenitor cells that can become T cells, and suggest that lymphoid progenitor cells in fetal liver concurrently undergo T- and B-specific molecular events within a single cell.
本研究已对存在于小鼠胎肝中的T淋巴细胞祖细胞进行了特征描述。第14天的胎肝含有祖细胞,通过悬滴培养将其转移至胸腺后可分化为成熟T细胞。胎肝细胞分级分离表明,T祖细胞局限于TER119-CD45+FcR(低)细胞中。令我们惊讶的是,TER119-CD45+FcR(低)胎肝细胞中的B220+而非B220-部分表现出产生T细胞的高效祖细胞活性。B220+胎肝细胞的祖细胞活性分别局限于T细胞、B细胞和巨噬细胞,频率约为分离出的B220+细胞的1/10、1/10和约1/20。B220+胎肝细胞不含有可检测到的TCR-β基因D-J重排,并且是c-kit+IL-7R+Thy-1-CD3-CD4(低)CD8-CD25-CD44+。B220+胎肝细胞表达编码TCR-β、pTα、Igα和VpreB的mRNA。有趣的是,在VDJ重排的TCR-β转基因小鼠中,B220+胎肝细胞表达TCRβ链,这表明转基因B220+胎肝细胞同时激活了TCR-β转录和B220表达。这些结果表明,B220由可成为T细胞的胎肝淋巴细胞祖细胞表达,并提示胎肝中的淋巴细胞祖细胞在单个细胞内同时经历T和B特异性分子事件。