Proteasome Inhibition Profoundly Affects Activated Human B Cells

Abstract

BACKGROUND: Proteasome inhibitors, although initially developed for the treatment of malignancies, have been found to affect normal plasma cells by efficaciously inducing apoptosis. One proteasome inhibitor, bortezomib, has been used in transplantation settings to deplete human leukocyte antigen antibody-producing plasma cells to reverse humoral allograft rejection. METHODS: To establish whether proteasome inhibitors are active on B cells, being plasma cell precursors, we examined a set of four proteasome inhibitors, including bortezomib, carfilzomib, ONX 0912, and ONX 0914, for their potential to impact the functionalities of activated B cells in vitro. RESULTS: All proteasome inhibitors dose-dependently abrogated IgM and IgG production by activated B cells, as well as their proliferation, with varying efficiencies. The bortezomib-induced decline in immunoglobulin production was mainly due to a decrease in the number of B cells capable of immunoglobulin secretion, caused by apoptosis. CONCLUSIONS: The action of proteasome inhibitors is not confined to plasma cells but also has impact on activated naïve and memory B cells.