Determinants of Human B Cell Migration Across Brain Endothelial Cells
Open accessAbstract
Circulating B cells enter the CNS as part of normal immune surveillance and in pathologic states, including the common and disabling illness multiple sclerosis. However, little is known about the molecular mechanisms that mediate human B cell interaction with the specialized brain endothelial cells comprising the blood-brain barrier (BBB). We studied the molecular mechanisms that regulate the migration of normal human B cells purified ex vivo, across human adult brain-derived endothelial cells (HBECs). We found that B cells migrated across HBECs more efficiently than T cells from the same individuals. B cell migration was significantly inhibited by blocking Abs to the adhesion molecules ICAM-1 and VLA-4, but not VCAM-1, similar to the results previously reported for T cells. Blockade of the chemokines monocyte chemoattractant protein-1 and IL-8, but not RANTES or IFN-gamma-inducible protein-10, significantly inhibited B cell migration, and these results were correlated with the chemokine receptor expression of B cells measured by flow cytometry and by RNase protection assay. Tissue inhibitor of metalloproteinase-1, a natural inhibitor of matrix metalloproteinases, significantly decreased B cell migration across the HBECs. A comprehensive RT-PCR comparative analysis of all known matrix metalloproteinases and tissue inhibitors of metalloproteinases in human B and T cells revealed distinct profiles of expression of these molecules in the different cell subsets. Our results provide insights into the molecular mechanisms that underlie human B cell migration across the BBB. Furthermore, they identify potential common, and unique, therapeutic targets for limiting CNS B cell infiltration and predict how therapies currently developed to target T cell migration, such as anti-VLA-4 Abs, may impact on B cell trafficking.
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Functional immune cells can enter the CNS through the blood-brain barrier, choroid plexus, and lymphatic vessels and have been described beyond neuropathological conditions.
“However, the idea that the CNS is an immune privileged organ has been reconsidered, as the functional immune cells can enter the CNS through the BBB, the choroid plexus, and the lymphatic vessels and have been described beyond neuropathological conditions (26, 35–47).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [39]
Bacterial products and metabolites can pass the blood-brain barrier and shape CNS development and functions and the genesis of certain diseases.
“Among the molecules that can pass the BBB are also bacterial products and metabolites shaping not only the CNS development and functions (6, 15) but also the genesis of certain diseases (33–42).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [39]
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- Authors
- Alter, A., Duddy, M., Hebert, S., Biernacki, K., Prat, A., Antel, J. P., Yong, V. W., Nuttall, R. K., Pennington, C. J., Edwards, D. R., & Bar-Or, A.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- University of Calgary (CA)
- University of East Anglia (GB)
- Neuroimmunology Unit, Montreal Neurological Institute , Montreal, Quebec ,
- Corresponding author
- Alter, Andrea
- Duddy, Martin
- Hebert, Sherry
- Biernacki, Katarzyna
- Prat, Alexandre
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-05-01
- Volume
- 170
- Issue
- 9
- Pages
- 4497-4505
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1803239093
- Cited by
- 195
- References
- 61
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 3 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 11 · 2018: 7 · 2017: 5 · 2016: 6 · 2015: 11 · 2014: 4 · 2013: 7 · 2012: 7
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Multiple Sclerosis Society of Canada
- Multiple Sclerosis Society
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Keywords
- B cell migration, blood-brain barrier, brain endothelial cells, multiple sclerosis, ICAM-1, VLA-4, chemokines, MCP-1, interleukin-8, chemokine receptors, TIMP-1, matrix metalloproteinases, B cell trafficking
- MeSH terms
- Adult, B-Lymphocytes, Blood-Brain Barrier, Cell Migration Inhibition, Cell Movement, Cell Separation, Endothelium, Vascular, Fibronectins, Humans, T-Lymphocytes, Diffusion Chambers, Culture, Interleukin-8, Chemokine CCL2, Vascular Cell Adhesion Molecule-1, Receptors, Chemokine, Tissue Inhibitor of Metalloproteinase-1, Matrix Metalloproteinases, Receptors, Interleukin-8A, Receptors, Interleukin-8B, Integrin alpha4beta1, Receptors, CCR2, Matrix Metalloproteinase Inhibitors
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