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The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging
Open accessAbstract
Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate B cell depletion is not fully understood. In particular, the anatomical location, the type of effector cells, and the mechanism underlying anti-CD20 therapy remain uncertain. Here, we found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, we established that, upon anti-CD20 treatment, Kupffer cells (KCs) mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. KCs were also effective in depleting malignant B cells in a model of spontaneous lymphoma. Our results identify Ab-dependent cellular phagocytosis by KCs as a primary mechanism of anti-CD20 therapy and provide an experimental framework for optimizing the efficacy of therapeutic Abs.
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Clynes, R. A., Towers, T. L., Presta, L. G., & Ravetch, J. V. (2000) · Nature Medicine · doi:10.1038/74704 · Cited by 2,768
Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene
Burnett, S. H., Kershen, E. J., Zhang, J., Zeng, L., Straley, S. C., Kaplan, A. M., & Cohen, D. A. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0903442 · Cited by 307
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Mass, E., Nimmerjahn, F., Kierdorf, K., & Schlitzer, A. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00848-y · Cited by 621
Overdijk, M. B., Verploegen, S., Bögels, M., van Egmond, M., van Bueren, J. J. L., Mutis, T., Groen, R. W., Breij, E., Martens, A. C., Bleeker, W. K., et al. (2015) · mAbs · doi:10.1080/19420862.2015.1007813 · Cited by 521
Garnelo, M., Tan, A., Her, Z., Yeong, J., Lim, C. J., Chen, J., Lim, K. H., Weber, A., Chow, P., Chung, A., et al. (2017) · Gut · doi:10.1136/gutjnl-2015-310814 · Cited by 461
The Dynamics of Apoptotic Cell Clearance
Elliott, M. R., & Ravichandran, K. S. (2016) · Developmental Cell · doi:10.1016/j.devcel.2016.06.029 · Cited by 319
Metadata
- Authors
- Montalvao, F., Garcia, Z., Celli, S., Breart, B., Deguine, J., Van Rooijen, N., & Bousso, P.
- Venue
- Journal of Clinical Investigation
- Published
- 2013-11-01
- Volume
- 123
- Issue
- 12
- Pages
- 5098-5103
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2160920639
- Cited by
- 192
- References
- 2
- FWCI
- 10.07
- Type
- journal article
- Language
- en
- Open access
- green
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- Montalvao, F., Garcia, Z., Celli, S., Breart, B., Deguine, J., Van Rooijen, N., & Bousso, P. (2013). The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging. Journal of Clinical Investigation. https://doi.org/10.1172/jci70972
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