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Memory B Cells and Long-lived Plasma Cells

机译:内存B细胞和长寿等离子体细胞

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摘要

The importance of B cell and antibody-mediated immune response in the acute and long-term persistence of transplanted solid organs has become increasingly evident in recent years. A variety of therapeutic innovations target antibodies directed toward HLA or blood groups (ABO) to allow better allocation and posttransplant longevity of organs. Antibodies originate from plasma cells (PCs), which are terminally differentiated B cells. Long-term production and persistence of these antibodies is partly due to fast reactivation of previously generated memory B cells; however, there is increasing evidence that some differentiated PCs can persist independently in the bone marrow for years or even decades, producing specific antibodies or even experiencing regeneration without proliferation without need to be replaced by newly differentiating B cells. This review outlines the currently presumed pathways of differentiation, antibody, and memory generation on both B-cell and PC levels. On this background, current therapeutic concepts for antibody reduction before and after solid organ transplantation are considered, to better understand their mechanisms, possible synergisms, and specific risks. Specific differences in regards to ABO versus HLA antibodies as well as practical relevance for generation of desensitization and posttransplant antibody-directed therapy protocols are discussed.
机译:近年来,B细胞和抗体介导的移植固体器官急性和长期持续性在急性和长期持续性中的重要性变得越来越明显。针对HLA或血液组(ABO)的各种治疗创新靶抗体,以便更好地分配和后翻转器官的寿命。抗体源自血浆细胞(PC),其是终端分化的B细胞。这些抗体的长期产量和持久性部分是由于先前产生的存储器B细胞的快速再活化;然而,有越来越多的证据表明,一些差异化的PC可以在骨髓中独立持续多年甚至数十年,产生特异性抗体甚至经历再生而不需要通过新分化的B细胞所取代而不需要替代。该审查概述了B细胞和PC水平上的分化,抗体和记忆产生的当前推定的途径。在此背景下,考虑了固体器官移植前后的抗体减少的当前治疗概念,以更好地理解其机制,可能的协同作用和特定风险。讨论了对ABO与HLA抗体的特定差异以及对脱敏和后翻转抗体抗体治疗方案的实际相关性。

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