Ying-Han ChenKimberly ZaldanaFrank YeungIvan Vujkovic-CvijinAlexander E. DownieJIAN-DA LINYi YangChristin HerrmannOyebola OyesolaFelix RozenbergRobert E. SchwartzDavid KimKurt TioYasmine BelkaidP’ng LokeAndrea L. GrahamSergei B. KoralovKen Cadwell2025-04-022025-04-022025-03-07https://www.scopus.com/record/display.uri?eid=2-s2.0-86000345324&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/726223Inbred 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.en[SDGs]SDG3[SDGs]SDG15journal article10.1126/sciadv.ads2364