Monocytes mediate shaving of B‐cell‐bound anti‐CD20 antibodies

Summary Anti‐CD20 monoclonal antibodies are promising for the treatment of B‐cell malignancies such as chronic lymphocytic leukaemia and autoimmune diseases where auto‐antibodies play an important role. Anti‐CD20 such as rituximab (RTX) mediates B‐cell depletion through mechanisms such as complement‐mediated cytotoxicity and antibody‐dependent cellular cytotoxicity. However, in haematological malignancies, such effector mechanisms can be saturated and result in release of malignant B cells with reduced levels of CD20. It has been hypothesized that this is the result of monocyte‐mediated shaving of the CD20/RTX complex from the B‐cell surface. Here, we confirm, that in vitro co‐culture of human monocytes and RTX‐labelled syngeneic B cells results in reduced expression of CD20/RTX complex on the B cell surface. This shaving mechanism was the result of active protease activity because EDTA and PMSF were able to mediate partial inhibition. Also, a series of alternative anti‐CD20 antibodies representing both type I and type II antibodies were tested for their ability to induce the shaving reaction. These results demonstrate that a monocyte‐mediated shaving reaction can lead to complete loss of most anti‐CD20 antibodies from the surface of B cells even from healthy donors and this is an important obstacle for antibody‐mediated immune therapy. The findings demonstrate the necessity of developing novel antibodies that maintain high effector functions without enabling activation of the shaving reaction.