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.

Bone loss and immune dysregulation are among the main adverse outcomes of spaceflight challenging astronauts' health and safety. However, consequences on B‐cell development and responses are still under‐investigated. To fill this gap, we used advanced proteomics analysis of femur bone and marrow to compare mice flown for 1 mo on board the BION‐M1 biosatellite, followed or not by 1 wk of recovery on Earth, to control mice kept on Earth. Our data revealed an adverse effect on B lymphopoiesis 1 wk after landing. This phenomenon was associated with a 41% reduction of B cells in the spleen. These reductions may contribute to explain increased susceptibility to infection even if our data suggest that flown animals can mount a humoral immune response. Future studies should investigate the quality/efficiency of produced antibodies and whether longer missions worsen these immune alterations.—Tascher, G., Gerbaix, M., Maes, P., Chazarin, B., Ghislin, S., Antropova, E., Vassilieva, G., Ouzren‐Zarhloul, N., gauquelin‐Koch, G., Vico, L., Frippiat, J.‐P., Bertile, F. Analysis of femurs from mice embarked on board BION‐M1 biosatellite reveals a decrease in immune cell development, including B cells, after 1 wk of recovery on Earth. FASEB J. 33, 3772–3783 (2019). http://www.fasebj.org

a b s t r a c tC3 is a component of the complement system that plays a central role in immunity, development and tissue regeneration. In this study, we isolated the C3 cDNA of the Iberian ribbed newt Pleurodeles waltl. This cDNA encodes a 1637 amino acid protein with an estimated molecular mass of 212.5 kDa. The deduced amino acid sequence showed that P. waltl C3 contains all the conserved domains known to be critical for C3 function. Quantitative real-time PCR (qRT-PCR) demonstrated that under normal physiological conditions, P. waltl C3 mRNA is expressed early during development because it is likely required for neurulation. Then, its expression increased as the immune system developed. In adults, the liver is the richest source of C3, though other tissues can also contribute. Further analysis of C3 expression demonstrated that C3 transcription increased when P. waltl larvae were exposed to pH or temperature stress, suggesting that environmental modifications might affect this animal's defenses against pathogens.