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The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging
- Source :
- Journal of Clinical Investigation, Journal of Clinical Investigation, 2013, 123 (12), pp.5098-5103. ⟨10.1172/JCI70972⟩, Journal of Clinical Investigation, American Society for Clinical Investigation, 2013, 123 (12), pp.5098-5103. ⟨10.1172/JCI70972⟩, 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, vol. 123, no. 12, pp. 5098-5103 . https://doi.org/10.1172/JCI70972, Journal of Clinical Investigation, 123(12), 5098-5103. The American Society for Clinical Investigation
- Publication Year :
- 2013
- Publisher :
- HAL CCSD, 2013.
-
Abstract
- International audience; 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.
- Subjects :
- MESH: Antigens, CD20
MESH: Antibodies, Monoclonal
Mice
0302 clinical medicine
MESH: Animals
MESH: Phagocytosis
B-Lymphocytes
0303 health sciences
Brief Report
Optical Imaging
Antibodies, Monoclonal
General Medicine
MESH: Fluorescent Dyes
Burkitt Lymphoma
Liver regeneration
3. Good health
medicine.anatomical_structure
Lymphatic system
Liver
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
MESH: Liver Regeneration
Antibody
Lymphoma, B-Cell
Kupffer Cells
Lymphoid Tissue
MESH: Mice, Transgenic
Phagocytosis
Mice, Transgenic
Biology
Lymphocyte Depletion
03 medical and health sciences
Antigen
In vivo
MESH: Mice, Inbred C57BL
MESH: B-Lymphocytes
medicine
Animals
MESH: Mice
B cell
Fluorescent Dyes
030304 developmental biology
MESH: Lymphoma, B-Cell
MESH: Lymphocyte Depletion
MESH: Optical Imaging
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Antigens, CD20
medicine.disease
Liver Regeneration
Lymphoma
Mice, Inbred C57BL
MESH: Burkitt Lymphoma
Disease Models, Animal
MESH: Kupffer Cells
Liposomes
Immunology
MESH: Lymphoid Tissue
Cancer research
biology.protein
MESH: Liposomes
Clodronic Acid
MESH: Disease Models, Animal
MESH: Liver
MESH: Clodronic Acid
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Investigation, Journal of Clinical Investigation, 2013, 123 (12), pp.5098-5103. ⟨10.1172/JCI70972⟩, Journal of Clinical Investigation, American Society for Clinical Investigation, 2013, 123 (12), pp.5098-5103. ⟨10.1172/JCI70972⟩, 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, vol. 123, no. 12, pp. 5098-5103 . https://doi.org/10.1172/JCI70972, Journal of Clinical Investigation, 123(12), 5098-5103. The American Society for Clinical Investigation
- Accession number :
- edsair.doi.dedup.....87e505499e988d6050dbe060931377e5