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Updated: May 11, 2026
08:49
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Proteasome inhibition profoundly affects activated human B cells.
Arend Mulder1, Sebastiaan Heidt, Manon Vergunst
1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. a.mulder@lumc.nl
Transplantation
|April 30, 2013
Summary
Proteasome inhibitors impact B cells, not just plasma cells. These drugs reduce B cell proliferation and immunoglobulin production, offering new therapeutic possibilities.
Area of Science:
- Immunology
- Pharmacology
Background:
- Proteasome inhibitors induce apoptosis in plasma cells, aiding in humoral allograft rejection reversal.
- Bortezomib is a proteasome inhibitor used in transplantation to deplete antibody-producing plasma cells.
Purpose of the Study:
- To investigate the effects of proteasome inhibitors on B cells, the precursors to plasma cells.
- To determine if proteasome inhibitors impact the function of activated B cells.
Main Methods:
- Four proteasome inhibitors (bortezomib, carfilzomib, ONX 0912, ONX 0914) were tested in vitro.
- The impact on activated B cell functionalities, including proliferation and immunoglobulin production, was assessed.
Main Results:
- All tested proteasome inhibitors dose-dependently reduced IgM and IgG production by activated B cells.
- Inhibition of B cell proliferation and immunoglobulin secretion was observed, with varying efficiencies.
- Bortezomib-induced reduction in immunoglobulin production was linked to increased apoptosis in B cells.
Conclusions:
- Proteasome inhibitors affect not only plasma cells but also activated naive and memory B cells.
- This suggests broader therapeutic potential for proteasome inhibitors beyond current applications.
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