Aging Induces an Nlrp3 Inflammasome-Dependent Expansion of Adipose B Cells That Impairs Metabolic Homeostasis

During aging, visceral adiposity is often associated with alterations in adipose tissue (AT) leukocytes, inflammation, and metabolic dysfunction. However, the contribution of AT B cells in immunometabolism during aging is unexplored. Here, we show that aging is associated with an expansion of a unique population of resident non-senescent aged adipose B cells (AABs) found in fat-associated lymphoid clusters (FALCs). AABs are transcriptionally distinct from splenic age-associated B cells (ABCs) and show greater expansion in female mice. Functionally, whole-body B cell depletion restores proper lipolysis and core body temperature maintenance during cold stress. Mechanistically, the age-induced FALC formation, AAB, and splenic ABC expansion is dependent on the Nlrp3 inflammasome. Furthermore, AABs express IL-1R, and inhibition of IL-1 signaling reduces their proliferation and increases lipolysis in aging. These data reveal that inhibiting Nlrp3-dependent B cell accumulation can be targeted to reverse metabolic impairment in aging AT. [Display omitted] •Adipose-resident aged B cells are increased in fat-associated lymphoid clusters (FALC)•Age-related FALC formation and B cell expansion are regulated by the Nlrp3 inflammasome•IL-1R signaling drives adipose B cell proliferation and impaired lipolysis•B cell depletion in aging restores lipolysis and improves cold tolerance Camell et al. identify unique resident aged adipose B cells (AABs) that impair generation of fatty-acid substrates needed for ATP production during fasting and diminish the ability to maintain proper core body temperature upon cold stress in aging. AAB accumulation and age-induced defects in lipolysis depend on Nlrp3 inflammasome and IL-1 signaling.