Hayakawa K, Tarlinton D, Hardy R R
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
J Immunol. 1994 May 15;152(10):4801-7.
Early B-lineage progenitor cells (Pro-B) isolated from murine fetal liver and adult bone marrow can differentiate to the immature B cell stage in a stromal cell-dependent culture system and to mature B cells upon transfer into immunodeficient SCID mice. By using immunofluorescence analysis, we found that progenitor cells from day 16 fetus differentiating in culture lacked MHC class II expression during the Pre-B and immature B cell stages, whereas such expression was readily apparent on the surface of corresponding adult-derived populations. RT-PCR analysis of RNA message levels for the four class II genes (A alpha, A beta, E alpha, E beta) yielded completely concordant results. B cells of fetal progeny did eventually express class II upon further maturation in vivo. Thus, the onset of class II expression is uniquely delayed during fetal B cell differentiation. This result explains an apparent paradox, i.e., that class II expression is absent from B cells in neonatal spleen but present as early as the Pre-B cell stage in adult bone marrow. Furthermore, we suggest that such distinct programs of class II expression during fetal and adult lymphopoiesis could result in differences in susceptibility to tolerance.
从鼠胎儿肝脏和成年骨髓中分离出的早期B谱系祖细胞（前B细胞），在基质细胞依赖的培养系统中可分化至未成熟B细胞阶段，并在转入免疫缺陷的SCID小鼠后分化为成熟B细胞。通过免疫荧光分析，我们发现，在培养中分化的16日龄胎儿的祖细胞在前B细胞和未成熟B细胞阶段缺乏MHC II类分子表达，而在相应的成年来源群体的表面这种表达则很明显。对四个II类基因（Aα、Aβ、Eα、Eβ）的RNA信息水平进行的RT-PCR分析得出了完全一致的结果。胎儿后代的B细胞在体内进一步成熟后最终确实表达了II类分子。因此，在胎儿B细胞分化过程中，II类分子表达的起始被独特地延迟了。这一结果解释了一个明显的矛盾现象，即新生脾脏中的B细胞缺乏II类分子表达，但在成年骨髓中早在前B细胞阶段就已存在。此外，我们认为，胎儿和成年淋巴细胞生成过程中这种独特的II类分子表达程序可能导致对耐受性的易感性差异。
