Monocytes mediate shaving of B-cell-bound anti-CD20 antibodies.

Abstract:

: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.

journal_name

Immunology

journal_title

Immunology

authors

Pedersen AE,Jungersen MB,Pedersen CD

doi

10.1111/j.1365-2567.2011.03434.x

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

239-45

issue

2

eissn

0019-2805

issn

1365-2567

journal_volume

133

pub_type

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