CD20-specific antibodies are a common therapy for B cell malignancies and autoimmune disorders, but the mechanism of the resulting B cell depletion has been unclear. This study shows that the liver has a central role. Using intravital two-photon imaging in mice and a fluorescence-tagged reporter to mark Kupffer cells, the authors showed that B cells circulating in the liver sinusoids arrested on Kupffer cells and were engulfed by these cells after injection with a CD20-specific monoclonal antibody. This process was impaired in mice lacking FcRγ, which shows that engagement of Fc receptors on Kupffer cells is required for antibody-dependent cellular phagocytosis of B cells. Kupffer cells were also shown to engulf spontaneously developing lymphoma cells in mice receiving CD20-specific antibody therapy. The authors predict that depletion of malignant lymphoid cells in humans will be more efficient for recirculating tumour cells than those in secondary lymphoid organs.
References
Montalvao, F. et al. The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging. J. Clin. Invest. http://dx.doi.org/10.1172/JCI70972 (2013)
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Minton, K. Kupffer cells mediate B cell depletion. Nat Rev Immunol 13, 849 (2013). https://doi.org/10.1038/nri3579
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DOI: https://doi.org/10.1038/nri3579