New J Stewart, King R Glenn, Kearney John F
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.
Immunol Rev. 2016 Mar;270(1):32-50. doi: 10.1111/imr.12397.
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 (NAbs) 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 NAb repertoire is therefore paramount. A more thorough understanding of NAb repertoire development holds promise for the design of both biological diagnostics and therapies. In this article, we review the development and functions of NAbs and examine three glycan specificities, represented in the innate-like B cell pool, to illustrate the complex roles environmental antigens play in NAb 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.
源自天然样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，并且在越来越多的过敏性和自身免疫性疾病中代表着一个有前景的治疗靶点。这些抗体通常具有自身反应性，并包含进化上保守的特异性，包括某些聚糖特异性抗体。尽管存在这种保守性，但在天然样B淋巴细胞发育过程中，通过自然暴露或免疫接种接触细菌多糖，会导致聚糖反应性B细胞库中的克隆组成发生显著变化。据报道，聚糖反应性天然抗体（NAb）在自身免疫性疾病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NAb库的组成和功能至关重要。更深入地了解NAb库的发育有望为生物诊断和治疗的设计提供依据。在本文中，我们回顾了NAb的发育和功能，并研究了天然样B细胞库中呈现的三种聚糖特异性，以说明环境抗原在NAb库发育中所起的复杂作用。我们还讨论了新生儿期和围产期天然样B细胞库克隆可塑性增加的影响，以及通过干预疗法靶向B细胞发育和纠正适应性免疫系统这一重要分支中的缺陷的前景。
