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Title: Migratory cues controlling B-lymphocyte trafficking in human lymph nodes.
Austin Authors: Park, Saem Mul;Brooks, Anna Es;Chen, Chun-Jen J;Sheppard, Hilary M;Loef, Evert Jan;McIntosh, Julie D;Angel, Catherine E;Mansell, Claudia J;Bartlett, Adam;Cebon, Jonathan S ;Birch, Nigel P;Dunbar, P Rod
Affiliation: School of Biological Sciences, The University of Auckland, Auckland, New Zealand
School of Medicine, The University of Auckland, Auckland, New Zealand
Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New Zealand
Olivia Newton-John Cancer Research Institute
La Trobe University School of Cancer Medicine, Heidelberg, Australia
Issue Date: Jan-2021
Date: 2020-09-15
Publication information: Immunology and Cell Biology 2021; 99(1): 49-64
Abstract: B-cell migration within lymph nodes (LNs) is crucial to adaptive immune responses. Chemotactic gradients are proposed to drive migration of B cells into follicles, followed by their relocation to specific zones of the follicle during activation, and ultimately egress. However, the molecular drivers of these processes and the cells generating chemotactic signals that affect B cells in human LNs are not well understood. We used immunofluorescence microscopy, flow cytometry and functional assays to study molecular mechanisms of B-cell migration within human LNs, and found subtle but important differences to previous murine models. In human LNs we find CXCL13 is prominently expressed at the follicular edge, often associated with fibroblastic reticular cells located in these areas, whereas follicular dendritic cells show minimal contribution to CXCL13 expression. Human B cells rapidly downregulate CXCR5 on encountering CXCL13, but recover CXCR5 expression in the CXCL13-low environment. These data suggest that the CXCL13 gradient in human LNs is likely to be different from that proposed in mice. We also identify CD68+ CD11c+ PU.1+ tingible body macrophages within both primary and secondary follicles as likely drivers of the sphingosine-1-phosphate (S1P) gradient that mediates B-cell egress from LNs, through their expression of the S1P-degrading enzyme, S1P lyase. Based on our findings, we present a model of B-cell migration within human LNs, which has both similarities and interesting differences to that proposed for mice.
DOI: 10.1111/imcb.12386
ORCID: 0000-0002-0999-0245
Journal: Immunology and Cell Biology
PubMed URL: 32740978
Type: Journal Article
Subjects: B-cell egress
B-cell migration
S1P lyase
fibroblastic reticular cells
human lymph node
Appears in Collections:Journal articles

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