Structure, Function, and Therapeutic Use of IgM Antibodies.
Structure, Function, and Therapeutic Use of IgM Antibodies.
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IgM抗体的结构、功能和治疗用途。
DOI：
10.3390/antib9040053
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发表时间：
2020-10-13
期刊：
影响因子：
--
通讯作者：
Peterson MS
中科院分区：
文献类型：
--
作者：
Keyt BA;Baliga R;Sinclair AM;Carroll SF;Peterson MS
天然免疫球蛋白M(IgM)抗体是五聚体或六聚体大分子免疫球蛋白，在进化过程中高度保守。IgM最初在B细胞个体发育过程中表达，是暴露于外来抗原后分泌的第一批抗体。IgM多聚体有10个(五聚体)或12个(六聚体)抗原结合域，由成对的重链和四个恒定结构域组成，每个结构域都有一个可变区，与相应的轻链配对。虽然天然的IgM抗体的抗原结合亲和力通常低于免疫球蛋白G，但它们的多价性允许高亲和力结合和有效结合补体以诱导补体依赖的细胞溶解。IgM抗体的高亲和力使其在结合低水平的抗原和非蛋白质抗原时特别有效，例如，微生物表面存在的碳水化合物或脂肪。五聚体IgM抗体还包含一个连接的(J)链，它稳定了五聚体结构，并能够与几个受体结合。其中一个这样的受体，聚合免疫球蛋白受体(PIgR)，负责从血管系统到肺和胃肠道的粘膜表面的跨细胞作用。几种自然产生的IgM抗体已被探索作为临床试验的治疗药物，一种新的分子，即具有增强结合和/或额外功能特性的工程IgM抗体正在人类身上进行评估。在这里，我们回顾了自80多年前发现IgM抗体以来，在对其生物学、结构、功能、制造和治疗潜力的理解方面取得的重大进展。
Natural immunoglobulin M (IgM) antibodies are pentameric or hexameric macro-immunoglobulins and have been highly conserved during evolution. IgMs are initially expressed during B cell ontogeny and are the first antibodies secreted following exposure to foreign antigens. The IgM multimer has either 10 (pentamer) or 12 (hexamer) antigen binding domains consisting of paired µ heavy chains with four constant domains, each with a single variable domain, paired with a corresponding light chain. Although the antigen binding affinities of natural IgM antibodies are typically lower than IgG, their polyvalency allows for high avidity binding and efficient engagement of complement to induce complement-dependent cell lysis. The high avidity of IgM antibodies renders them particularly efficient at binding antigens present at low levels, and non-protein antigens, for example, carbohydrates or lipids present on microbial surfaces. Pentameric IgM antibodies also contain a joining (J) chain that stabilizes the pentameric structure and enables binding to several receptors. One such receptor, the polymeric immunoglobulin receptor (pIgR), is responsible for transcytosis from the vasculature to the mucosal surfaces of the lung and gastrointestinal tract. Several naturally occurring IgM antibodies have been explored as therapeutics in clinical trials, and a new class of molecules, engineered IgM antibodies with enhanced binding and/or additional functional properties are being evaluated in humans. Here, we review the considerable progress that has been made regarding the understanding of biology, structure, function, manufacturing, and therapeutic potential of IgM antibodies since their discovery more than 80 years ago.
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影响因子：
5
作者：
Butler M;Meneses-Acosta A
通讯作者：
Meneses-Acosta A
影响因子：
5.4
作者：
Choi, Youn Soo;Dieter, Jacquelyn A.;Rothaeusler, Kristina;Luo, Zheng;Baumgarth, Nicole
通讯作者：
Baumgarth, Nicole
影响因子：
11.4
作者：
CATTANEO, A;NEUBERGER, MS
通讯作者：
NEUBERGER, MS
DOI：
10.1111/ajt.12698
发表时间：
2014-06
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Flechner SM;Mulgoankar S;Melton LB;Waid TH;Agarwal A;Miller SD;Fokta F;Getts MT;Frederick TJ;Herrman JJ;Puisis JP;O'Toole L;Sung R;Shihab F;Wiseman AC;Getts DR
通讯作者：
Getts DR
新范式：从板凳到诊所的IGM：2011年11月15日至16日，德国法兰克福。
影响因子：
5.3
作者：
Hanala S
通讯作者：
Hanala S