Identification and characterization of CXCL13 producers in bone tissue in response to fasting

The bone tissue serves as a dynamic reservoir that accommodates diverse immune cell populations during low-energy states such as fasting. Energy-restriction and reduced metabolism induce a transient migration of naïve B cells from Peyer's patches to the bone marrow in mice, a process driven by the upregulation of Cxcl13 expression within the bone niche. However, the specific cellular source of CXCL13 and the upstream signals regulating its expression remain undefined. Our analysis identified the lineage-negative fraction of the bone as the major source of CXCL13. Single-cell RNA sequencing of these cells further demonstrated that Cxcl13 was selectively expressed by osteogenic mesenchymal stromal cells (MSCs) during fasting. Consistently, immunofluorescence imaging showed an increased frequency of these CXCL13-producing cells under fasting conditions, primarily localized within the perivascular niche. Gene ontology analysis of differentially expressed genes in these cells during fasting revealed enrichment of TGF-β and PPAR signaling. In line with this, pharmacological intervention in either the TGF-β or PPARγ signaling pathway significantly attenuated fasting-induced naïve B-cell migration and CXCL13 production in the bone. These results establish a mechanistic link between systemic metabolic cues and the bone marrow immune microenvironment. We propose that osteogenic MSCs play a vital role in orchestrating this trafficking program for naïve B cells, underscoring a dynamic crosstalk between the bone stromal cells and the immune system.