The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging

Fabricio Montalvao (1) , Zacarias Garcia (1) , Susanna Celli (1) , Béatrice Breart (1) , Jacques Deguine (1) , Nico van Rooijen (2) , Philippe Bousso (1)

1 Dynamiques des Réponses immunes - Dynamics of Immune Responses
2 VU University Medical Center [Amsterdam]

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.

Domains: Life Sciences [q-bio]; Immunology; Life Sciences [q-bio]; Human health and pathology; Hépatology and Gastroenterology

Fabricio Montalvao, Zacarias Garcia, Susanna Celli, Béatrice Breart, Jacques Deguine, et al.. The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging. Journal of Clinical Investigation, 2013, 123 (12), pp.5098 - 5103. ⟨10.1172/JCI70972⟩. ⟨pasteur-01410108⟩