Natural Antibodies as Rheostats for Susceptibility to Chronic Diseases in the Aged

Abstract

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.

Germline V repertoires: Origin, maintenance, diversification

“…This is the way it appears. The production of natural antibodies is part of the normal healthy physiology of vertebrate organisms B‐non‐0: The B1a and B2 lines (MZ, FO) to varying degrees provide the truly antigen‐driven conventional B clonal repertoire of VLVH‐D that is generated after birth and expresses the somatically derived repertoire.…”

Relationship of Autoantibodies to MDA-LDL and ApoB-Immune Complexes to Sex, Ethnicity, Subclinical Atherosclerosis, and Cardiovascular Events

“…Conversely, as IgMs are thought to be derived from B-1 cells present at birth or shortly thereafter, a decline in titers to OSE over time may suggest loss of certain B-1 cell subsets, resulting in decreased innate immune responses to chronic diseases caused by OSE and certain infections. 13,21,28–30 Consistent with a genetic influence of circulating autoantibodies to OSE, a recent genome-wide linkage study and genetic association in twins, the heritability (h 2 ) of IgM MDA-LDL and IgM apoB-IC were 0.69 and 0.80, respectively, and for IgG MDA-LDL and apoB-IC was 0.62 and 0.53, respectively, which was similar or higher than physiological, inflammatory, or lipid traits. 16 …”

Selective breeding on natural antibodies in chickens

“…NAb are defined as antigen binding antibodies present in individuals without a previous exposure to this antigen. NAb play an essential role in the innate and adaptive immunity against self-antigens and various types of pathogens, and are contributing to healthy aging and disease resistance (Zhou et al, 2007;Panda et al, 2015;Rothstein, 2016). Different NAb isotypes are found: predominantly IgM, but also IgA, and IgG (Baumgarth et al, 2015;Rothstein, 2016).…”

“…NAb play an essential role in the innate and adaptive immunity against self-antigens and various types of pathogens, and are contributing to healthy aging and disease resistance (Zhou et al, 2007;Panda et al, 2015;Rothstein, 2016). Different NAb isotypes are found: predominantly IgM, but also IgA, and IgG (Baumgarth et al, 2015;Rothstein, 2016). In earlier studies, high NAb levels (especially IgM) binding the overt antigen keyhole limpet hemocyanin (KLH) were related to lower mortality of commercial layer chickens (Star et al, 2007a;Sun et al, 2011;Wondmeneh et al, 2015).…”