Plasticity of the human IgM repertoire in response to a long-term spaceflight

Immune dysregulation is among the main adverse outcomes of spaceflight. Despite its crucial role in host protection effects on the human antibody repertoire are unknown. Consequently we examined the IgM repertoire of five cosmonauts 25 days before launch after 64 and 129 days spent on the International Space Station (ISS) and after 1 7 and 30 days of Earth reambulation using high-throughput sequencing. This is the first study of this kind. Our data revealed that the IgM repertoire of cosmonauts was different from the one of control subjects already prior to launch and that 2 out the 5 analyzed cosmonauts presented significant changes of their IgM repertoire during the mission. These modifications persisted up to 30 days after landing likely affected the specificities of IgM binding sites correlated with changes of the V(D)J recombination process in charge of creating functional antibody genes and coincided with a higher stress response. These data confirm that about half of the astronauts who spent six months on the ISS are subjected to immunological changes contribute to explain increased susceptibility to infection reveal individual responses and consequently that personalized approaches should be implemented during future deep-space exploration missions that will endure for an unprecedented amount of time.