Abstract
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.
Highlights
Hypergravity exposure during gestation modifies the TCRb repertoire of newborn mice Stephanie Ghislin*, Nassima Ouzren-Zarhloul*, Sandra Kaminski & Jean-Pol Frippiat
Concerning B lymphopoiesis, we have recently shown that the transcription of IgM heavy chains and of the Ikaros lymphoid-determining transcription factor are modified when embryos of the urodele amphibian Pleurodeles waltl develop under altered gravity conditions
We showed that a long-term spaceflight affects the use of immunoglobulin heavy chain variable gene segments (VH) subgroups[5] and the expression of individual VH gene segments[6] in response to an antigenic stimulation in adult P. waltl, thereby suggesting that these conditions could affect the V(D)J recombination machinery
Summary
Hypergravity exposure during gestation modifies the TCRb repertoire of newborn mice Stephanie Ghislin*, Nassima Ouzren-Zarhloul*, Sandra Kaminski & Jean-Pol Frippiat. Two of these factors are interesting because they increase the diversity of antigen-binding sites at the level of the third complementarity determining region (CDR3) of TCR heavy chains These factors are Artemis which can create palindromes when it opens DNA hairpins and the terminal deoxynucleotidyl transferase (Tdt) which add nucleotides (N-nucleotides) at open extremities of coding segments before their joining[1]. This assembling procedure, called V(D)J recombination, takes place at specific stages of B and T cell differentiation and is essential for lymphocyte differentiation and the generation of diverse BCR and TCR repertoires indispensable for protection against pathogens. We showed that a long-term spaceflight affects the use of immunoglobulin heavy chain variable gene segments (VH) subgroups[5] and the expression of individual VH gene segments[6] in response to an antigenic stimulation in adult P. waltl, thereby suggesting that these conditions could affect the V(D)J recombination machinery
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