Bortezomib affects the function of human B cells: possible implications for desensitization protocols.
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.
Dept. of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
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S
Heidt
D L
DL
Roelen
M
M
Vergunst
I I N
II
Doxiadis
F H J
FH
Claas
A
A
Mulder
D018941:Antigens, CD19 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D001771:Blood Banks; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D003888:Desensitization, Immunologic / Q000379:methods*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects; D007075:Immunoglobulin M / Q000097:blood / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*
D018941:Antigens, CD19; D001323:Autoantibodies; D001897:Boronic Acids; D006680:HLA Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib