Reyneveld G IJsbrand, Savelkoul Huub F J, Parmentier Henk K
Faculty of Science, VU University, Amsterdam, Netherlands.
Adaptation Physiology Group, Department of Animal Sciences, Wageningen University, Wageningen, Netherlands.
Front Immunol. 2020 Sep 10;11:2139. doi: 10.3389/fimmu.2020.02139. eCollection 2020.
Natural antibodies (NAb) are defined as germline encoded immunoglobulins found in individuals without (known) prior antigenic experience. NAb bind exogenous (e.g., bacterial) and self-components and have been found in every vertebrate species tested. NAb likely act as a first-line immune defense against infections. A large part of NAb, so called natural autoantibodies (NAAb) bind to and clear (self) neo-epitopes, apoptotic, and necrotic cells. Such self-binding antibodies cannot, however, be considered as pathogenic autoantibodies in the classical sense. IgM and IgG NAb and NAAb and their implications in health and disease are relatively well-described in humans and mice. NAb are present in veterinary (and wildlife) species, but their relation with diseases and disorders in veterinary species are much less known. Also, there is little known of IgA NAb. IgA is the most abundant immunoglobulin with essential pro-inflammatory and homeostatic properties urging for more research on the importance of IgA NAb. Since NAb in humans were indicated to fulfill important functions in health and disease, their role in health of veterinary species should be investigated more often. Furthermore, it is unknown whether levels of NAb-isotypes and/or idiotypes can and should be modulated. Veterinary species as models of choice fill in a niche between mice and (non-human) primates, and the study of NAb in veterinary species may provide valuable new insights that will likely improve health management. Below, examples of the involvement of NAb in several diseases in mostly humans are shown. Possibilities of intravenous immunoglobulin administration, targeted immunotherapy, immunization, diet, and genetic modulation are discussed, all of which could be well-studied using animal models. Arguments are given why veterinary immunology should obtain inspiration from human studies and why human immunology would benefit from veterinary models. Within the One concept, findings from veterinary (and wildlife) studies can be related to human studies and so that both fields will mutually benefit. This will lead to a better understanding of NAb: their origin, activation mechanisms, and their implications in health and disease, and will lead to novel health management strategies for both human and veterinary species.
天然抗体（NAb）被定义为在没有（已知）先前抗原接触经历的个体中发现的种系编码免疫球蛋白。NAb可结合外源性（如细菌）和自身成分，并且在所有已测试的脊椎动物物种中均有发现。NAb可能作为抵御感染的一线免疫防御。很大一部分NAb，即所谓的天然自身抗体（NAAb），可结合并清除（自身）新表位、凋亡细胞和坏死细胞。然而，这种自身结合抗体在传统意义上不能被视为致病性自身抗体。IgM和IgG NAb以及NAAb及其在人类和小鼠健康与疾病中的意义已有相对充分的描述。NAb存在于兽医（和野生动物）物种中，但它们与兽医物种疾病和病症的关系却鲜为人知。此外，关于IgA NAb的了解也很少。IgA是最丰富的免疫球蛋白，具有重要的促炎和稳态特性，因此迫切需要对IgA NAb的重要性进行更多研究。由于已表明人类中的NAb在健康和疾病中发挥重要作用，因此应更频繁地研究它们在兽医物种健康中的作用。此外，尚不清楚NAb同种型和/或独特型的水平是否以及应否被调节。兽医物种作为理想的模型填补了小鼠和（非人类）灵长类动物之间的空白，对兽医物种中NAb的研究可能会提供有价值的新见解，这可能会改善健康管理。以下展示了NAb在主要是人类的几种疾病中的参与情况示例。讨论了静脉注射免疫球蛋白、靶向免疫疗法、免疫接种、饮食和基因调节的可能性，所有这些都可以使用动物模型进行深入研究。阐述了兽医免疫学应从人类研究中获取灵感以及人类免疫学将从兽医模型中受益的原因。在“同一概念”内，兽医（和野生动物）研究的结果可与人类研究相关联，从而使两个领域相互受益。这将有助于更好地理解NAb：它们的起源、激活机制以及它们在健康和疾病中的意义，并将为人类和兽医物种带来新的健康管理策略。
