Effects of spaceflight on the immunoglobulin repertoire of unimmunized C57BL/6 mice

Abstract

Spaceflight has been shown to suppress the adaptive immune response, altering the distribution and function of lymphocyte populations. B lymphocytes express highly specific and highly diversified receptors, known as immunoglobulins (Ig), that directly bind and neutralize pathogens. Ig diversity is achieved through the enzymatic splicing of gene segments within the genomic DNA of each B cell in a host. The collection of Ig specificities within a host, or Ig repertoire, has been increasingly characterized in both basic research and clinical settings using high-throughput sequencing technology (HTS). We utilized HTS to test the hypothesis that spaceflight affects the B-cell repertoire. To test this hypothesis, we characterized the impact of spaceflight on the unimmunized Ig repertoire of C57BL/6 mice that were flown aboard the International Space Station (ISS) during the Rodent Research One validation flight in comparison to ground controls. Individual gene segment usage was similar between ground control and flight animals, however, gene segment combinations and the junctions in which gene segments combine was varied among animals within and between treatment groups. We also found that spontaneous somatic mutations in the IgH and Igκ gene loci were not increased. These data suggest that space flight did not affect the B cell repertoire of mice flown and housed on the ISS over a short period of time.

Characterization of the naive murine antibody repertoire using unamplified high-throughput sequencing

“…To minimize potential single animal aberrations and repertoire skewing, we pooled splenic tissue of four unimmunized mice in three biological replicates. This approach was successful since we saw less variation with pooled samples compared to data sets that are made up of single mice [ 61 ]. Grieff et al .…”

“…We also wanted some background data about the Ig repertoire in the normal B6 mouse population. Knowing that there can be significant mouse-to-mouse variability in the Ig repertoire [ 36 , 61 ] and to minimize the impact any one mouse might have in the validation data set, we chose to pool multiple mice specifically for these validation experiments [ 35 ]. We now present these data on the splenic repertoire of conventionally housed, unimmunized, unchallenged, adult C57BL/6J mice.…”

Gut Microbiome and Space Travelers’ Health: State of the Art and Possible Pro/Prebiotic Strategies for Long-Term Space Missions

“…These cells appear to be minimally involved during spaceflight, since their frequency does not change during flight but seems to be reduced on return to Earth (Tascher et al, 2019). No changes in the immunoglobulin repertoire were observed in mice (Ward et al, 2018) and space travelers studies (Stowe et al, 1999;Rykova et al, 2008). The variations observed in T lymphocytes are more complex.…”

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

“…In the same way, another study showed that the antibody repertoire of mice flown to and housed on the ISS over a short period of time (21-22 days) was not affected. 49 However, the analysis of associations involving the most expressed IGHV subgroups and the most expressed IGHJ segments revealed that some specific associations (IGHV3-48 with IGHJ5 and IGHV3-23 with IGHJ6) are altered in all the cosmonauts. Interestingly, IGHV3-48 and IGHV3-23 belong to the top 10 of the expressed IGHV segments and IGHJ6 is the second most frequently used IGHJ gene segment in the blood of healthy human adults.…”