The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.
The innate mononuclear phagocyte network depletes B lymphocytes through Fc receptor-dependent mechanisms during anti-CD20 antibody immunotherapy.
复制标题
在抗 CD20 抗体免疫治疗期间，先天单核吞噬细胞网络通过 Fc 受体依赖性机制耗尽 B 淋巴细胞。
DOI：
10.1084/jem.20040119
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发表时间：
2004-06-21
期刊：
影响因子：
--
通讯作者：
Tedder TF
中科院分区：
文献类型：
--
作者：
Uchida J;Hamaguchi Y;Oliver JA;Ravetch JV;Poe JC;Haas KM;Tedder TF
抗CD20抗体免疫疗法可有效治疗非霍奇金淋巴瘤和自身免疫性疾病。然而，由于人类机制研究的局限性，B细胞耗尽的细胞和分子途径仍然不清楚。已提出的机制包括抗体、效应细胞和补体依赖的细胞毒性，破坏CD20信号通路，以及诱导细胞凋亡。为了确定体内B细胞耗竭的机制，利用12株代表所有4种免疫球蛋白G亚型的小鼠抗鼠CD20单抗，建立了一种新的抗CD20免疫治疗小鼠模型。抗CD20抗体以一种完全依赖于效应细胞Fc受体表达的同型限制性方式迅速耗尽绝大多数循环和组织B细胞。B细胞耗竭使用了FcγRI和FcγRIII依赖的途径，而在Fcr普通γ链缺陷小鼠中，B细胞没有被消除。单核细胞是B细胞耗竭的主要效应细胞，对T细胞和自然杀伤细胞没有明显的作用。虽然大多数抗CD20抗体在体外激活补体，但B细胞耗竭对于C3、C4或C1q补体成分遗传缺陷的小鼠是完全有效的。在抗γ免疫治疗过程中，天然单核细胞网络通过Fc CD20受体依赖的途径耗尽B细胞，这对抗CD20和其他基于抗体的治疗具有重要的临床意义。
Anti-CD20 antibody immunotherapy effectively treats non-Hodgkin's lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined because human mechanistic studies are limited. Proposed mechanisms include antibody-, effector cell–, and complement-dependent cytotoxicity, the disruption of CD20 signaling pathways, and the induction of apoptosis. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti–mouse CD20 monoclonal antibodies representing all four immunoglobulin G isotypes. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion used both FcγRI- and FcγRIII-dependent pathways, whereas B cells were not eliminated in FcR common γ chain–deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or natural killer cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3, C4, or C1q complement components. That the innate monocyte network depletes B cells through FcγR-dependent pathways during anti-CD20 immunotherapy has important clinical implications for anti-CD20 and other antibody-based therapies.
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补体激活有选择地增强高亲和力抗雄激素自身抗体的IgG2b和IgG3同种型的致病性。
影响因子：
15.3
作者：
Azeredo da Silveira, Samareh;Kikuchi, Shuichi;Fossati-Jimack, Liliane;Moll, Thomas;Saito, Takashi;Verbeek, J Sjef;Botto, Marina;Walport, Mark J;Carroll, Michael;Izui, Shozo
通讯作者：
Izui, Shozo
影响因子：
20.3
作者：
Bellosillo, B;Villamor, N;Montserrat, E
通讯作者：
Montserrat, E
影响因子：
15.3
作者：
Fossati-Jimack, L;Reininger, L;Izui, S
通讯作者：
Izui, S
影响因子：
3.4
作者：
Demidem, A;Lam, T;Bonavida, B
通讯作者：
Bonavida, B
影响因子：
2.2
作者：
GazzanoSantoro, H;Ralph, P;Mukku, VR
通讯作者：
Mukku, VR