Rothstein Thomas L
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research , Manhasset, NY , USA.
Front Immunol. 2016 Apr 7;7:127. doi: 10.3389/fimmu.2016.00127. eCollection 2016.
Natural antibodies are spontaneously produced in the absence of infection or immunization, and are both anti-microbial and autoreactive. Autoreactive natural antibodies can bind noxious molecules, such as those involved in clinical situations of atherosclerosis (oxLDL), malignancy (NGcGM3), and neurodegeneration (amyloid, tau) and can affect the fate of their targets or the cells bearing them to maintain homeostasis. Clinically relevant natural antibodies have been shown to decline with advancing age in those few situations where measurements have been made. Consistent with this, human B-1 cells that are thought to be responsible for generating natural antibodies also decline with advancing age. These findings together suggest that an age-related decline in amount or efficacy of homeostatic natural antibodies is associated with relative loss of protection against molecules involved in several diseases whose incidence rises in the older age population, and that those individuals experiencing greatest loss are at greatest risk. In this view, natural antibodies act as rheostats for susceptibility to several age-related diseases. These considerations suggest that administration of natural antibodies, or of factors that maintain B-1 cells and/or enhance production of natural antibodies by B-1 cells, may serve to counteract the onset or progression of age-related chronic illness.
天然抗体在没有感染或免疫的情况下自发产生，具有抗微生物和自身反应性。自身反应性天然抗体可结合有害分子，如参与动脉粥样硬化（氧化低密度脂蛋白）、恶性肿瘤（N-乙酰神经氨酸神经节苷脂GM3）和神经退行性变（淀粉样蛋白、tau蛋白）临床情况的分子，并可影响其靶标或携带这些靶标的细胞的命运以维持体内平衡。在少数已进行测量的情况下，临床相关天然抗体已显示会随着年龄增长而下降。与此一致的是，被认为负责产生天然抗体的人类B-1细胞也会随着年龄增长而减少。这些发现共同表明，稳态天然抗体数量或效力的与年龄相关的下降与针对几种在老年人群中发病率上升的疾病所涉及分子的保护作用相对丧失有关，而且那些丧失最多的个体风险最大。从这个角度来看，天然抗体充当了对几种与年龄相关疾病易感性的调节器。这些考虑因素表明，给予天然抗体或维持B-1细胞和/或增强B-1细胞产生天然抗体的因子，可能有助于抵消与年龄相关的慢性疾病的发生或进展。
