Bortezomib Affects the Function of Human B Cells: Possible Implications for Desensitization Protocols.

Heidt S, Roelen DL, Vergunst M, Doxiadis II, Claas FH, Mulder A.

Clinical Transplants 2009, Chapter 35

Abstract

Bortezomib is a potent inducer of apoptosis in malignant as well as non-malignant human plasma cells. Recently, bortezomib has come to attention for the treatment of humoral rejection. As bortezomib is a proteasome inhibitor, it likely affects other cell types, such as activated B cells, as well. Since additional anti-B cell effects could be beneficial for the treatment of humoral rejection, we tested whether bortezomib inhibited human B cell function. When B cells were activated in a CD40 mAb driven culture system, bortezomib dose-dependently abrogated their IgM and IgG production as well as their proliferation. This bortezomib induced inhibition was caused by induction of apoptosis, since levels of caspase 3/7 activity were increased. In addition to its effects on plasma cells, bortezomib profoundly inhibits activated human B cells. This finding suggests that when bortezomib is used for desensitization or for the treatment of humoral rejection, there is no need for additional anti-B cell therapy, such as anti-CD20 mAb (Rituximab) treatment.