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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Immune cell trafficking among blood, lymphoid organs, and tissues is essential for homeostasis; however, the influence of environmental stressors on steady-state distribution remains unclear. Here we show that ambient cold stress (4 \u00b0C) and dexamethasone treatment induced systemic leukocytopenia, marked by the selective depletion of circulating B cells and reduced splenic mass. Viability assays confirmed that this loss was not due to cell death. Adoptive transfer of fluorescently labeled leukocytes revealed the directed redistribution of B cells into the bone marrow (BM). Regarding the mechanism, cold stress elevated corticosterone, which upregulated the homing receptor C-X-C chemokine receptor 4 (CXCR4) on peripheral B cells. Blocking CXCR4 with AMD3100 markedly impaired BM migration, establishing the pathway\u2019s functional necessity. This work proposed a model in which the BM acts as a transient immune reservoir during stress, conserving energy by sequestering B cells in a protected niche while prioritizing thermogenesis. This paradigm offers new insight into homeostatic immune regulation and potential therapeutic strategies for B-cell-mediated autoimmune disease.<\/jats:p>","DOI":"10.3390\/ijms27188214","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:33:42Z","timestamp":1789479222000},"page":"8214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ambient Cold Exposure Modulates B-Cell Distribution via Glucocorticoid-CXCR4 Signaling"],"prefix":"10.3390","volume":"27","author":[{"given":"Hsuan-Yun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te-Sheng","family":"Lien","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1994-7355","authenticated-orcid":false,"given":"Der-Shan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3176-6274","authenticated-orcid":false,"given":"Guan-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-0146","authenticated-orcid":false,"given":"Ching-Feng","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"},{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko-Nien","family":"Shih","sequence":"additional","affiliation":[{"name":"Department of Medical Image and Radiological Technology, Yuanpei University of Medical Technology, Hsinchu City 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8731-3485","authenticated-orcid":false,"given":"Hsin-Hou","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.immuni.2025.01.013","article-title":"Integrated control of leukocyte compartments as a feature of adaptive physiology","volume":"58","author":"Jaschke","year":"2025","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e202302465","DOI":"10.26508\/lsa.202302465","article-title":"CXCR4: From B-cell development to B cell-mediated diseases","volume":"7","author":"Giorgiutti","year":"2024","journal-title":"Life Sci. 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