Manipulation of the glycan-specific natural antibody repertoire for immunotherapy.
Manipulation of the glycan-specific natural antibody repertoire for immunotherapy.
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DOI：
10.1111/imr.12397
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发表时间：
2016-03
影响因子：
8.7
通讯作者：
Kearney JF
中科院分区：
文献类型：
--
作者：
New JS;King RG;Kearney JF
来自先天样B淋巴细胞的天然免疫球蛋白在抑制炎症反应中发挥重要作用，在越来越多的过敏性和自身免疫性疾病中代表了一个有希望的治疗靶点。这些抗体通常是自身反应性的，并包含进化上保守的特异性，包括某些聚糖特异性抗体。尽管如此，在先天样B淋巴细胞发育过程中暴露于细菌多糖，无论是通过自然暴露还是免疫，都会引起多糖反应性B细胞池中克隆表现的显着变化。聚糖反应性天然抗体已被报道在自身免疫性和炎症性疾病中发挥保护和致病作用。因此，了解健康的聚糖反应性天然抗体库的组成和功能是至关重要的。对天然抗体库发展的更彻底的了解为生物诊断和治疗的设计带来了希望。在本文中，我们回顾了天然抗体的发展和功能，并检查了先天样B细胞池中代表的三种聚糖特异性，以说明环境抗原在天然抗体库发展中发挥的复杂作用。我们还讨论了新生儿和围产期先天样B细胞库克隆可塑性增加的意义，以及通过介入治疗靶向B细胞发育和纠正这一适应性免疫系统重要臂缺陷的前景。
Natural immunoglobulin derived from innate-like B lymphocytes plays important roles in the suppression of inflammatory responses and represents a promising therapeutic target in a growing number of allergic and autoimmune diseases. These antibodies are commonly autoreactive and incorporate evolutionarily conserved specificities, including certain glycan-specific antibodies. Despite this conservation, exposure to bacterial polysaccharides during innate-like B lymphocyte development, through either natural exposure or immunization, induces significant changes in clonal representation within the glycan-reactive B cell pool. Glycan-reactive natural antibodies have been reported to play protective and pathogenic roles in autoimmune and inflammatory diseases. An understanding of the composition and functions of a healthy glycan-reactive natural antibody repertoire is therefore paramount. A more thorough understanding of natural antibody repertoire development holds promise for the design of both biological diagnostics and therapies. In this article we review the development and functions of natural antibodies and examine three glycan specificities, represented in the innate-like B cell pool, to illustrate the complex roles environmental antigens play in natural antibody repertoire development. We also discuss the implications of increased clonal plasticity of the innate-like B cell repertoire during neonatal and perinatal periods, and the prospect of targeting B cell development with interventional therapies and correct defects in this important arm of the adaptive immune system.