Ambient Cold Exposure Modulates B-Cell Distribution via Glucocorticoid-CXCR4 Signaling

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 °C) 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's 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.