Natural antibodies (nAbs) are most commonly defined as immunoglobulins present in the absence of pathological conditions or deliberate immunizations. Occurrence of nAbs in germ- and antigen-free mice suggest that their production is driven, at least in part, by self-antigens. Accordingly, nAbs are constituted of natural autoantibodies (nAAbs), and can belong to the IgM, IgG, or IgA subclasses. These nAbs provide immediate protection against infection while the adaptive arm of the immune system mounts a specific and long-term response. Beyond immediate protection from infection, nAbs have been shown to play various functional roles in the immune system, which include clearance of apoptotic debris, suppression of autoimmune and inflammatory responses, regulation of B cell responses, selection of the B cell repertoires, and regulation of B cell development. These various functions of nAbs are afforded by their reactivity, which is broad, cross-reactive, and shown to recognize evolutionarily fixed epitopes shared between foreign and self-antigens. Furthermore, nAbs have unique characteristics that also contribute to their functional roles and set them apart from antigen-specific antibodies. In further support for the role of nAbs in the protection against infections and in the maintenance of immune homeostasis, the therapeutic preparation of polyclonal immunoglobulins, intravenous immunoglobulin (IVIG), rich in nAbs is commonly used in the replacement therapy of primary and secondary immunodeficiencies and in the immunotherapy of a large number of autoimmune and inflammatory diseases. Here, we review several topics on nAbs features and functions, and therapeutic applications in human diseases.

中文翻译：

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天然抗体：从针对病原体的一线防御到永久性免疫稳态。

天然抗体（nAbs）最常见的定义是在没有病理状况或故意免疫的情况下存在的免疫球蛋白。在不含细菌和抗原的小鼠中，nAb的出现表明它们的产生至少部分受自身抗原的驱动。因此，nAb由天然自身抗体（nAAb）构成，并且可以属于IgM，IgG或IgA亚类。这些nAb可为感染提供即时保护，而免疫系统的适应性臂则可产生特定的长期响应。除了直接保护免受感染外，nAb已显示在免疫系统中发挥各种功能作用，包括清除凋亡碎片，抑制自身免疫和炎症反应，调节B细胞反应，选择B细胞库，和调节B细胞发育。nAb的这些不同功能是由它们的反应性提供的，它们具有广泛的交叉反应性，并且可以识别外源抗原和自身抗原之间共享的进化固定表位。此外，nAb具有独特的特征，这些特征也有助于其功能作用，并使它们与抗原特异性抗体区分开。为了进一步支持nAb在预防感染和维持免疫稳态中的作用，富含nAb的多克隆免疫球蛋白，静脉免疫球蛋白（IVIG）的治疗性制剂通常用于原发性和继发性免疫缺陷和在大量自身免疫和炎性疾病的免疫治疗中 在这里，我们回顾了有关nAbs特性和功能的几个主题，