The Rap GTPases Regulate B Cell Morphology, Immune-Synapse Formation, and Signaling by Particulate B Cell Receptor Ligands
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B lymphocytes spread and extend membrane processes when searching for antigens and form immune synapses upon contacting cells that display antigens on their surface. Although these dynamic morphological changes facilitate B cell activation, the signaling pathways underlying these processes are not fully understood. We found that activation of the Rap GTPases was essential for these changes in B cell morphology. Rap activation was important for B cell receptor (BCR)- and lymphocyte-function-associated antigen-1 (LFA-1)-induced spreading, for BCR-induced immune-synapse formation, and for particulate BCR ligands to induce localized F-actin assembly and membrane-process extension. Rap activation and F-actin assembly were also required for optimal BCR signaling in response to particulate antigens but not soluble antigens. Thus by controlling B cell morphology and cytoskeletal organization, Rap might play a key role in the activation of B cells by particulate and cell-associated antigens.
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Similar defects in B cell immune synapses likely underlie poor antibody responses after vaccination or infection in HEM1-deficient patients.
“Similar defects in B cell immune synapses likely underlie poor antibody responses after vaccination or infection [9, 38].”
From HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions (2022) · cites this paper as [38]
The Results (page unavailable) show that blocking Rap activation impaired immune-synapse formation in experimental B cells. The paper does not study HEM1-deficient patients or establish that synapse defects underlie their poor antibody responses after vaccination or infection. (LLM, conf=0.87)
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Cited by
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HEM1 Actin Immunodysregulatory Disorder: Genotypes, Phenotypes, and Future Directions
Cook, S., Lenardo, M. J., & Freeman, A. F. (2022) · Journal of Clinical Immunology · doi:10.1007/s10875-022-01327-0 · Cited by 24 · see citing works
- Authors
- Lin, K. B. L., Freeman, S. A., Zabetian, S., Brugger, H., Weber, M., Lei, V., Dang-Lawson, M., Tse, K. W. K., Santamaria, R., Batista, F. D., & Gold, M. R.
- Affiliations
- University of British Columbia (CA)
- Cancer Research UK (GB)
- Corresponding author
- Gold, Michael R.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 28
- Issue
- 1
- Pages
- 75-87
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2086285294
- Cited by
- 105
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- 2025: 4 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 2 · 2015: 7 · 2014: 3 · 2013: 6 · 2012: 5
- FWCI
- 6.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
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- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael Smith Health Research BC
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Rap GTPases, immune synapse formation, B cell receptor signaling, particulate antigen, LFA-1, F-actin assembly, cytoskeleton, B cell activation
- MeSH terms
- Actins, Animals, B-Lymphocytes, Cell Line, Enzyme Activation, Humans, Lymphocyte Activation, Microscopy, Electron, Scanning, Receptors, Antigen, B-Cell, Signal Transduction, Antigen Presentation, Microscopy, Confocal, rap GTP-Binding Proteins, Mice
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