Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Transplantation. 2013 Jun 15;95(11):1331-7. doi: 10.1097/TP.0b013e3182911739.
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.
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.
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.
The action of proteasome inhibitors is not confined to plasma cells but also has impact on activated naïve and memory B cells.
蛋白酶体抑制剂最初是为治疗恶性肿瘤而开发的，但已被发现通过有效诱导细胞凋亡来影响正常浆细胞。一种蛋白酶体抑制剂硼替佐米已被用于移植环境中，以耗尽产生人类白细胞抗原抗体的浆细胞，从而逆转体液移植物排斥反应。
为了确定蛋白酶体抑制剂是否对作为浆细胞前体的 B 细胞具有活性，我们研究了一组四种蛋白酶体抑制剂，包括硼替佐米、卡非佐米、ONX 0912 和 ONX 0914，以评估它们对体外激活 B 细胞功能的潜在影响。
所有蛋白酶体抑制剂均呈剂量依赖性地消除了激活的 B 细胞产生的 IgM 和 IgG，以及它们的增殖，效率不同。硼替佐米诱导的免疫球蛋白产生下降主要是由于能够分泌免疫球蛋白的 B 细胞数量减少，这是由细胞凋亡引起的。
蛋白酶体抑制剂的作用不仅局限于浆细胞，还对激活的幼稚和记忆 B 细胞有影响。
