Hypergravity exposure during gestation modifies the TCRβ repertoire of newborn mice

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 TCR beta 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 TCR beta 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 TCR beta transcripts to study the impact of hypergravity on TCR beta diversity. Our data show that hypergravity exposure increases the transcription of TCR beta chains, and of genes whose products are involved in TCR signaling, and affects the V(D) J recombination process. We also observed that similar to 85% of the TCR beta 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.