Abstract This Pillars of Immunology article is a commentary on “A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice,” a pivotal article written by Hao Y, O’Neill P, Naradikian MS, Scholz JL, and Cancro MP, and published in Blood in 2011 (PMID: 21562046; PMCID: PMC3152496).