Abstract
Abstract Immune mechanisms of human and murine diseases of aging include generation of chronic inflammation and autoimmunity. We and others have associated aging in mice and humans with increased chronic inflammation, reduced vaccine response and an increase in a B lymphocyte subset referred to as Age-associated B cells (ABCs) in mice and DN (double negative) in humans. Immune cell function is dependent on metabolic pathways and to date understudied. A. In this work we sorted splenic ABCs (CD19+AA4.1-CD21-CD23−) from young (3–4 months) and old (18–22 months) C57BL/6 mice showing an increased percentage in old and increased RNA expression of SASP (senescence-associated secretory phenotype) pro-inflammatory cytokines (TNFa, IL-6), proinflammatory micro-RNAs (miRs 155 and 16) and cell cycle regulators p16INK4 and p21Waf1 in old ABCs. We also show here old B cells produce more autoimmune IgG antibodies (to MDA, malondialdehyde and ADA, adipocyte-derived antigens), ABCs more than FO (follicular), and ABCs from old more than those from young. Total B cells and ABCs from old mice also have a higher metabolic profile compared with those of young mice. B. The frequency of DN cells is increased in human elderly as well as those younger with obesity. Plasma of obese had more autoantibodies to dsDNA, MDA, and ADA and the DN B cells showed higher levels of IA (Immune activation) markers and transcription factors, e.g. tbx21 (TBET) associated with autoimmunity. We have recently found that elderly human B cells are, like murine, hypermetabolic and are discovering possible mechanisms, such as fatty acids. Supported by grants from NIH (AG32576, AG059719, and AG023717)
