Rewilding catalyzes maturation of the humoral immune system
Inbred mice used for biomedical research display an underdeveloped immune system compared with adult humans, which is attributed in part to the artificial laboratory environment. Despite representing a central component of adaptive immunity, the impact of the laboratory environment on the B cell compartment has not been investigated in detail. Here, we performed an in-depth examination of B cells following rewilding, the controlled release of inbred laboratory mice into an outdoor enclosure. In rewilded mice, we observed B cells in circulation with increased signs of maturation, alongside heightened germinal center responses within secondary lymphoid organs. Rewilding also expanded B cells in the gut, which was accompanied by elevated systemic levels of immunoglobulin G (IgG) and IgM antibodies reactive to the microbiota. Our findings indicate that exposing laboratory mice to a more natural environment enhances B cell development to better reflect the immune system of free-living mammals.
Authors
- Ying-Han Chen (ORCID: https://orcid.org/0000-0002-6720-8610)
- Andrea L. Graham (ORCID: https://orcid.org/0000-0002-6580-2755)
- Oyebola O. Oyesola (ORCID: https://orcid.org/0000-0002-5347-7502)
- David D. Kim (ORCID: https://orcid.org/0000-0002-7528-0014)
- Ivan Vujkovic-Cvijin (ORCID: https://orcid.org/0000-0002-8611-4900)
- Alexander E. Downie (ORCID: https://orcid.org/0000-0002-6743-620X)
- Jian-Da Lin (ORCID: https://orcid.org/0000-0003-3697-4766)
- Robert E. Schwartz (ORCID: https://orcid.org/0000-0002-5417-5995)
- Ken Cadwell (ORCID: https://orcid.org/0000-0002-5860-0661)
- P’ng Loke (ORCID: https://orcid.org/0000-0002-6211-3292)
- Felix D. Rozenberg (ORCID: https://orcid.org/0000-0002-5532-9773)
- Frank Yeung (ORCID: https://orcid.org/0000-0002-1944-706X)
- Yasmine Belkaid (ORCID: https://orcid.org/0000-0001-9962-3571)
- Kimberly Zaldaña (ORCID: https://orcid.org/0009-0002-0300-5176)
- Sergei B. Koralov (ORCID: https://orcid.org/0000-0002-4843-3791)
- Christin Herrmann (ORCID: https://orcid.org/0000-0003-4885-1384)
- Yi Yang (ORCID: https://orcid.org/0000-0002-5200-0614)
- Kurt Tio
Institutions
- Cedars-Sinai Medical Center (US)
- National Institutes of Health (US)
- Santa Fe Institute (US)
- Institut Pasteur (FR)
- National Taiwan University (TW)
- SUNY Downstate Health Sciences University (US)
- Princeton University (US)
- Cornell University (US)
- Institute of Biomedical Sciences, Academia Sinica (TW)
- Max Planck Institute for Evolutionary Anthropology (DE)
- National Institute of Allergy and Infectious Diseases (US)
- Weill Cornell Medicine (US)
- New York University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-03-07
- DOI
- https://doi.org/10.1126/sciadv.ads2364
- Citations
- 9
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 7.25