Antibodies like Rituximab can remove cells in a variety of ways, including killing cells directly, inducing cell suicide, or triggering killing by other immune cells and molecules. Rituximab binds to CD20, a protein found on the surface of all B lymphocytes. In humans it is difficult to analyze how this leads to the elimination of B lymphocytes as only small numbers of cells can be sampled from the blood.
To mimic the clinical situation, Thomas Tedder and colleagues treated mice with a panel of antibodies specific for mouse CD20 (Rituximab is an antibody that binds to human but not mouse B cells). The antibodies that were effective in removing B cells did so by allowing B cell recognition by specialized 'scavenger' immune cells known as macrophages, which carry antibody receptors on their surface.
Less than half of patients with lymphoma respond to anti-CD20 therapy, so drugs that increase the number of macrophages or levels of antibody receptors might improve the response to Rituximab.
The new insight into how CD20 antibodies remove B cells should allow the design of better therapies not only for lymphoma, but also autoimmune diseases caused by rogue self-reactive B cells (as in rheumatoid arthritis), in which CD20 antibody trials are already underway.
Contact: Dr. Thomas F. Tedder, Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA, 919-684-3578, thomas.tedder@duke.edu .
Journal of Experimental Medicine