title: The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging.
abstract: 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.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Montalvao
authors.forename: Zacarias
authors.initials: Z
authors.lastname: Garcia
authors.forename: Susanna
authors.initials: S
authors.lastname: Celli
authors.forename: Béatrice
authors.initials: B
authors.lastname: Breart
authors.forename: Jacques
authors.initials: J
authors.lastname: Deguine
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000473:pathology*; D002051:Burkitt Lymphoma; D004002:Clodronic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D007728:Kupffer Cells / Q000502:physiology* / Q000648:ultrastructure; D008081:Liposomes; D008099:Liver / Q000276:immunology*; D008115:Liver Regeneration; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D061848:Optical Imaging / Q000379:methods*; D010587:Phagocytosis
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D005456:Fluorescent Dyes; D008081:Liposomes; D004002:Clodronic Acid