Ghislin Stéphanie, Ouzren-Zarhloul Nassima, Kaminski Sandra, Frippiat Jean-Pol
EA7300, Stress Immunity Pathogens Laboratory, Faculty of Medicine, Lorraine University, F-54500 Vandœuvre-lès-Nancy, France.
Sci Rep. 2015 Mar 20;5:9318. doi: 10.1038/srep09318.
During spaceflight, organisms are subjected to mechanical force changes (gravity (G) changes) that affect the immune system. However, gravitational effects on lymphopoiesis have rarely been studied. Consequently, we investigated whether the TCRβ repertoire, created by V(D)J recombination during T lymphopoiesis, is affected by hypergravity exposure during murine development. To address this question, C57BL/6j mice were mated in a centrifuge so that embryonic development, birth and TCRβ rearrangements occurred at 2G. Pups were sacrificed at birth, and their thymus used to quantify transcripts coding for factors required for V(D)J recombination and T lymphopoiesis. We also created cDNA mini-libraries of TCRβ transcripts to study the impact of hypergravity on TCRβ diversity. Our data show that hypergravity exposure increases the transcription of TCRβ chains, and of genes whose products are involved in TCR signaling, and affects the V(D)J recombination process. We also observed that ~85% of the TCRβ repertoire is different between hypergravity and control pups. These data indicate that changing a mechanical force (the gravity) during ontogeny will likely affect host immunity because properties of loops constituting TCR antigen-binding sites are modified in hypergravity newborns. The spectrum of peptides recognized by TCR will therefore likely be different.
在太空飞行期间，生物体受到影响免疫系统的机械力变化（重力（G）变化）。然而，重力对淋巴细胞生成的影响鲜有研究。因此，我们研究了在T淋巴细胞生成过程中由V（D）J重排产生的TCRβ库是否受小鼠发育期间超重力暴露的影响。为解决这个问题，将C57BL/6j小鼠置于离心机中交配，以使胚胎发育、出生和TCRβ重排在2G条件下发生。幼崽在出生时被处死，其胸腺用于定量编码V（D）J重排和T淋巴细胞生成所需因子的转录本。我们还创建了TCRβ转录本的cDNA微型文库，以研究超重力对TCRβ多样性的影响。我们的数据表明，超重力暴露会增加TCRβ链以及其产物参与TCR信号传导的基因的转录，并影响V（D）J重排过程。我们还观察到，超重力幼崽和对照幼崽之间约85%的TCRβ库不同。这些数据表明，个体发育过程中机械力（重力）的改变可能会影响宿主免疫，因为在超重力新生小鼠中构成TCR抗原结合位点的环的特性发生了改变。因此，TCR识别的肽谱可能会有所不同。
