title: CXCR4 promotes B cell egress from Peyer's patches.
abstract: Peyer's patches (PPs) play a central role in supporting B cell responses against intestinal antigens, yet the factors controlling B cell passage through these mucosal lymphoid tissues are incompletely understood. We report that, in mixed chimeras, CXCR4-deficient B cells accumulate in PPs compared with their representation in other lymphoid tissues. CXCR4-deficient B cells egress from PPs more slowly than wild-type cells, whereas CXCR5-deficient cells egress more rapidly. The CXCR4 ligand, CXCL12, is expressed by cells adjacent to lymphatic endothelial cells in a zone that abuts but minimally overlaps with the CXCL13(+) follicle. CXCR4-deficient B cells show reduced localization to these CXCL12(+) perilymphatic zones, whereas CXCR5-deficient B cells preferentially localize in these regions. By photoconverting KikGR-expressing cells within surgically exposed PPs, we provide evidence that naive B cells transit PPs with an approximate residency half-life of 10 h. When CXCR4 is lacking, KikGR(+) B cells show a delay in PP egress. In summary, we identify a CXCL12(hi) perilymphatic zone in PPs that plays a role in overcoming CXCL13-mediated retention to promote B cell egress from these gut-associated lymphoid tissues.
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology & Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Schmidt
authors.forename: Oliver
authors.initials: O
authors.lastname: Bannard
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Gray
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism; D054382:Chemokine CXCL13 / Q000276:immunology / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010581:Peyer's Patches / Q000276:immunology* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000276:immunology* / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000276:immunology / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; C513179:CXCR5 protein, mouse; D054377:Chemokine CXCL12; D054382:Chemokine CXCL13; C515256:Cxcl12 protein, mouse; C486386:Cxcl13 protein, mouse; D019718:Receptors, CXCR4; D054380:Receptors, CXCR5