Am"B"valent: anti-CD20 antibodies unravel the dual role of B cells in immunopathogenesis.

Accumulating evidence has designated B cells as central players in the pathogenesis of immune diseases. In the late 1990s, anti-CD20 monoclonal antibodies were developed for the treatment of B-cell non-Hodgkin lymphomas, offering the opportunity to efficiently deplete the B-cell compartment for therapeutic immunointerventions. Several studies have since established the beneficial effect of this drug on the course of a wide range of immune diseases. However, paradoxically, it has also been reported that rituximab sometimes worsens the symptoms of the very same conditions. The explanation that reconciles such apparently conflicting results has recently emerged from basic studies, which demonstrate that (1) B cells are also endowed with immune-regulatory properties and (2) the opposing contributions of B cells may overlap during the course of the disease. Caution should therefore be exercised when considering B-cell depletion because the therapeutic effect will depend on the relative contributions of the opposing B-cell activities at the time of the drug administration.