Hindlimb Unloading, a Physiological Model of Microgravity, Modifies the Murine Bone Marrow IgM Repertoire in a Similar Manner As Aging but Less Strongly

Overview

Journal Immun Ageing

Publisher Biomed Central

Specialty Geriatrics

Date 2023 Nov 21

PMID 37986079

Authors

Coralie Fonte

Pauline Jacob

Anne Vanet

Stephanie Ghislin

Jean-Pol Frippiat

Affiliations

Soon will be listed here.

Abstract

Background: The spaceflight environment is an extreme environment that affects the immune system of approximately 50% of astronauts. With planned long-duration missions, such as the deployment of the Lunar Gateway and possible interplanetary missions, it is mandatory to determine how all components of the immune system are affected, which will allow the establishment of countermeasures to preserve astronaut health. However, despite being an important component of the immune system, antibody-mediated humoral immunity has rarely been investigated in the context of the effects of the space environment. It has previously been demonstrated that 30 days aboard the BION-M1 satellite and 21 days of hindlimb unloading (HU), a model classically used to mimic the effects of microgravity, decrease murine B lymphopoiesis. Furthermore, modifications in B lymphopoiesis reported in young mice subjected to 21 days of HU were shown to be similar to those observed in aged mice (18-22 months). Since the primary antibody repertoire composed of IgM is created by V(D) J recombination during B lymphopoiesis, the objective of this study was to assess the degree of similarity between changes in the bone marrow IgM repertoire and in the V(D)J recombination process in 2.5-month-old mice subjected to 21 days of HU and aged (18 months) mice.

Results: We found that in 21 days, HU induced changes in the IgM repertoire that were approximately 3-fold less than those in aged mice, which is a rapid effect. Bone remodeling and epigenetics likely mediate these changes. Indeed, we previously demonstrated a significant decrease in tibial morphometric parameters from day 6 of HU and a progressive reduction in these parameters until day 21 of HU, and it has been shown that age and microgravity induce epigenetic changes.

Conclusion: These data reveal novel immune changes that are akin to advanced aging and underline the importance of studying the effects of spaceflight on antibody-mediated humoral immunity.

Citing Articles

Challenges for the human immune system after leaving Earth.

Marchal S, Chouker A, Bereiter-Hahn J, Kraus A, Grimm D, Kruger M NPJ Microgravity. 2024; 10(1):106.

PMID: 39557881 PMC: 11574097. DOI: 10.1038/s41526-024-00446-9.

Synergistic interplay between radiation and microgravity in spaceflight-related immunological health risks.

Wadhwa A, Moreno-Villanueva M, Crucian B, Wu H Immun Ageing. 2024; 21(1):50.

PMID: 39033285 PMC: 11264846. DOI: 10.1186/s12979-024-00449-w.

References

Buchheim J, Matzel S, Rykova M, Vassilieva G, Ponomarev S, Nichiporuk I . Stress Related Shift Toward Inflammaging in Cosmonauts After Long-Duration Space Flight. Front Physiol. 2019; 10:85. PMC: 6401618. DOI: 10.3389/fphys.2019.00085. View

Guerrettaz L, Johnson S, Cambier J . Acquired hematopoietic stem cell defects determine B-cell repertoire changes associated with aging. Proc Natl Acad Sci U S A. 2008; 105(33):11898-902. PMC: 2515225. DOI: 10.1073/pnas.0805498105. View

Wang C, Liu Y, Xu L, Jackson K, Roskin K, Pham T . Effects of aging, cytomegalovirus infection, and EBV infection on human B cell repertoires. J Immunol. 2013; 192(2):603-11. PMC: 3947124. DOI: 10.4049/jimmunol.1301384. View

Schatz D, Swanson P . V(D)J recombination: mechanisms of initiation. Annu Rev Genet. 2011; 45:167-202. DOI: 10.1146/annurev-genet-110410-132552. View

Johnston C, Wood A, Bolland D, Corcoran A . Complete sequence assembly and characterization of the C57BL/6 mouse Ig heavy chain V region. J Immunol. 2006; 176(7):4221-34. DOI: 10.4049/jimmunol.176.7.4221. View

Fonte C, Kaminski S, Vanet A, Lanfumey L, Cohen-Salmon C, Ghislin S . Socioenvironmental stressors encountered during spaceflight partially affect the murine TCR-β repertoire and increase its self-reactivity. FASEB J. 2018; 33(1):896-908. DOI: 10.1096/fj.201800969R. View

Pulivarthy S, Lion M, Kuzu G, Matthews A, Borowsky M, Morris J . Regulated large-scale nucleosome density patterns and precise nucleosome positioning correlate with V(D)J recombination. Proc Natl Acad Sci U S A. 2016; 113(42):E6427-E6436. PMC: 5081657. DOI: 10.1073/pnas.1605543113. View

Mourcin F, Breton C, Tellier J, Narang P, Chasson L, Jorquera A . Galectin-1-expressing stromal cells constitute a specific niche for pre-BII cell development in mouse bone marrow. Blood. 2011; 117(24):6552-61. DOI: 10.1182/blood-2010-12-323113. View

Lescale C, Schenten V, Djeghloul D, Bennabi M, Gaignier F, Vandamme K . Hind limb unloading, a model of spaceflight conditions, leads to decreased B lymphopoiesis similar to aging. FASEB J. 2014; 29(2):455-63. DOI: 10.1096/fj.14-259770. View

10.

Erdeljan P, MacDonald J, Matthews S . Glucocorticoids and serotonin alter glucocorticoid receptor (GR) but not mineralocorticoid receptor (MR) mRNA levels in fetal mouse hippocampal neurons, in vitro. Brain Res. 2001; 896(1-2):130-6. DOI: 10.1016/s0006-8993(01)02075-3. View

11.

Xu C, Schaffer L, Head S, Feeney A . Reciprocal patterns of methylation of H3K36 and H3K27 on proximal vs. distal IgVH genes are modulated by IL-7 and Pax5. Proc Natl Acad Sci U S A. 2008; 105(25):8685-90. PMC: 2438410. DOI: 10.1073/pnas.0711758105. View

12.

Rettig T, Bye B, Nishiyama N, Hlavacek S, Ward C, Pecaut M . Effects of skeletal unloading on the antibody repertoire of tetanus toxoid and/or CpG treated C57BL/6J mice. PLoS One. 2019; 14(1):e0210284. PMC: 6336310. DOI: 10.1371/journal.pone.0210284. View

13.

Aviles H, Belay T, Fountain K, Vance M, Sonnenfeld G . Increased susceptibility to Pseudomonas aeruginosa infection under hindlimb-unloading conditions. J Appl Physiol (1985). 2003; 95(1):73-80. DOI: 10.1152/japplphysiol.00968.2002. View

14.

Labrie 3rd J, Borghesi L, Gerstein R . Bone marrow microenvironmental changes in aged mice compromise V(D)J recombinase activity and B cell generation. Semin Immunol. 2005; 17(5):347-55. DOI: 10.1016/j.smim.2005.05.012. View

15.

Gong M, Li X, Zheng A, Xu H, Xie S, Yan R . Age-related changes in the TRB and IGH repertoires in healthy adult males and females. Immunol Lett. 2021; 240:71-76. DOI: 10.1016/j.imlet.2021.10.002. View

16.

Montefiori L, Wuerffel R, Roqueiro D, Lajoie B, Guo C, Gerasimova T . Extremely Long-Range Chromatin Loops Link Topological Domains to Facilitate a Diverse Antibody Repertoire. Cell Rep. 2016; 14(4):896-906. PMC: 4975037. DOI: 10.1016/j.celrep.2015.12.083. View

17.

Tascher G, Gerbaix M, Maes P, Chazarin B, Ghislin S, Antropova E . 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. 2018; 33(3):3772-3783. DOI: 10.1096/fj.201801463R. View

18.

Gaignier F, Schenten V, Bittencourt M, Gauquelin-Koch G, Frippiat J, Legrand-Frossi C . Three weeks of murine hindlimb unloading induces shifts from B to T and from th to tc splenic lymphocytes in absence of stress and differentially reduces cell-specific mitogenic responses. PLoS One. 2014; 9(3):e92664. PMC: 3963916. DOI: 10.1371/journal.pone.0092664. View

19.

Lescale C, Dias S, Maes J, Cumano A, Szabo P, Charron D . Reduced EBF expression underlies loss of B-cell potential of hematopoietic progenitors with age. Aging Cell. 2010; 9(3):410-9. DOI: 10.1111/j.1474-9726.2010.00566.x. View

20.

Pahwa R, Modak M, McMorrow T, Pahwa S, Fernandes G, GOOD R . Terminal deoxynucleotidyl transferase (TdT) enzyme in thymus and bone marrow. I. Age-associated decline of TdT in humans and mice. Cell Immunol. 1981; 58(1):39-48. DOI: 10.1016/0008-8749(81)90147-7. View