Bortezomib affects the function of human B cells: possible implications for desensitization protocols.

Area of Science:

• Immunology
• Pharmacology
• Transplantation

Background:

• Bortezomib, a proteasome inhibitor, induces apoptosis in plasma cells and is used for humoral rejection treatment.
• Its effects on activated B cells, crucial in humoral rejection, are not fully understood.
• Investigating bortezomib's impact on B cells could optimize humoral rejection therapies.

Purpose of the Study:

• To determine if bortezomib inhibits human B cell function.
• To assess the potential of bortezomib as a standalone therapy for humoral rejection.

Main Methods:

• Human B cells were activated using a CD40 mAb-driven culture system.
• Bortezomib's effects on B cell proliferation, IgM, and IgG production were measured.
• Apoptosis induction was assessed by measuring caspase 3/7 activity.

Main Results:

• Bortezomib demonstrated dose-dependent inhibition of B cell proliferation, IgM, and IgG production.
• This inhibition was attributed to bortezomib-induced apoptosis, evidenced by increased caspase 3/7 activity.
• Bortezomib profoundly inhibits activated human B cells, similar to its effect on plasma cells.

Conclusions:

• Bortezomib exhibits significant anti-B cell activity, including apoptosis induction in activated B cells.
• These findings suggest bortezomib monotherapy may be effective for humoral rejection treatment.
• Additional anti-B cell therapies, like anti-CD20 mAb, may not be necessary when using bortezomib.