Distinct patterns of expression of MHC class I and beta 2-microglobulin transcripts at early stages of mouse development.

Distinct patterns of expression of MHC class I and beta 2-microglobulin transcripts at early stages of mouse development.
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DOI:
10.4049/jimmunol.147.8.2740
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发表时间:
1991-10
影响因子:
4.4
通讯作者:
Leah Jaffe;E. Robertson;E. Bikoff
Leah Jaffe;E. Robertson;E. Bikoff
中科院分区:
医学2区
文献类型:
--
作者:
Leah Jaffe;E. Robertson;E. Bikoff

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在组织移植排斥反应中识别的I类表面抗原由一个40-45 kDa的H链和一个12 kDa的L链--β2-微球蛋白(β2M)组成。早期发育过程中MHC基因表达的调控被认为在同种异体胎儿移植的母体耐受中起着重要作用。在这里,我们使用原位杂交技术来表征MHC-I类mRNA在发育中的小鼠胚胎中表达的时间和空间模式。在初级和次级滋养层巨细胞群中,最初在性交后9.5天检测到MHC-I类转录本。在这个阶段,发育中的胎盘中剩余的胎儿成分都不表达MHC-I类mRNA。相比之下,滋养层巨细胞的外区是发育中的胎盘中唯一不表达可检测到的β2m mRNA水平的滋养外胚层组织。这些结果表明,MHC-I类基因和β-2M基因在移植后早期胚胎中的表达并不是协调调节的。此外,我们还利用多能胚胎干细胞在体外研究了MHC-I和β-2M基因表达的发育调控。采用悬浮培养技术可诱导ES细胞分化为内胚层样细胞。与维甲酸处理的F9细胞相比,ES细胞来源的内胚层表达高水平的β2m mRNA,但没有检测到MHC I类转录本。这些发现与我们的原位杂交实验结果一致,该实验结果表明,在活体内脏内胚层的衍生物中,β2M mRNA高水平表达,而MHC I类转录产物表达极弱。
The class I surface Ag recognized during tissue graft rejection are composed of a 40- to 45-kDa H chain and a 12-kDa L chain, beta 2-microglobulin (beta 2m). Regulation of MHC gene expression during early development is thought to play an essential role in maternal tolerance of the fetal allograft. Here we used in situ hybridization techniques to characterize the temporal and spatial pattern of expression of MHC class I mRNA in the developing mouse embryo. MHC class I transcripts were initially detected at day 9.5 postcoitus in the primary and secondary trophoblast giant cell populations. At this stage, none of the remaining fetal components of the developing placenta expresses MHC class I mRNA. By contrast, the outer zone of trophoblast giant cells is the only trophectoderm-derived tissue in the developing placenta that does not express detectable levels of beta 2m mRNA. These findings indicate that the onset of MHC class I and beta 2m gene expression in early postimplantation stage embryos is not coordinately regulated. In addition, we made use of pluripotent embryonic stem (ES) cells to study developmental regulation of MHC class I and beta 2m gene expression in vitro. ES cells can be induced to form endoderm-like cells by the technique of suspension culture. In contrast to retinoic acid-treated F9 cells, the endoderm derived from ES cells expressed high levels of beta 2m mRNA, but no detectable MHC class I transcripts. These findings are consistent with results of our in situ hybridization experiments showing high levels of expression of beta 2m mRNA, and extremely weak expression of MHC class I transcripts in derivatives of the visceral endoderm in vivo.