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Migratory cues controlling B-lymphocyte trafficking in human lymph nodes
Saem Mul Park1,2, Anna Es Brooks1,2, Chun-Jen J Chen1,2
1School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
Immunology and Cell Biology
|August 3, 2020
Summary
Human B-cell migration in lymph nodes involves distinct chemokine gradients. Tingible body macrophages drive B-cell egress via sphingosine-1-phosphate gradients, differing from mouse models.
Area of Science:
- Immunology
- Cell Biology
Background:
- B-cell migration within lymph nodes (LNs) is vital for adaptive immunity.
- The molecular drivers and signaling cells influencing human B-cell migration remain incompletely understood.
- Existing models are largely based on murine studies, with potential differences in humans.
Purpose of the Study:
- To investigate the molecular mechanisms and cellular sources of chemotactic signals guiding B-cell migration in human LNs.
- To compare B-cell migration dynamics in human LNs with established murine models.
- To elucidate the roles of specific chemokines and gradients in B-cell homing, activation, and egress.
Main Methods:
- Immunofluorescence microscopy
- Flow cytometry
- Functional assays
Main Results:
- CXCL13 is primarily expressed at the follicular edge by fibroblastic reticular cells, not follicular dendritic cells, in human LNs.
- Human B cells dynamically regulate CXCR5 expression in response to CXCL13 gradients.
- CD68+ CD11c+ PU.1+ tingible body macrophages express S1P lyase, suggesting their role in the sphingosine-1-phosphate (S1P) gradient mediating B-cell egress.
Conclusions:
- Human B-cell migration within LNs exhibits unique features compared to murine models, particularly regarding CXCL13 gradients.
- Tingible body macrophages are identified as key players in regulating B-cell egress through S1P signaling.
- A novel model for B-cell migration in human LNs is proposed, highlighting species-specific mechanisms.
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