Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection
Cory A. Perugino, Hang Liu, Jared Feldman, Jess Marbourg, Thomas V. Guy, Anson Hui, Nicole Ingram, Julian Liebaert, Neha Chaudhary, Weiyang Tao, Catherine Jacob-Dolan, Blake M. Hauser, Zayd Mian, Anusha Nathan, Zezhou Zhao, Clarety Kaseke, Rhoda Tano-Menka, Matthew A. Getz, Fernando Senjobe, Cristhian Berrios, Onosereme Ofoman, Zachary Manickas-Hill, Duane R. Wesemann, Jacob E. Lemieux, Marcia B. Goldberg, Kerstin Nündel, Ann M. Moormann, Ann Marshak‐Rothstein, Regina C. LaRocque, Edward T. Ryan, John Iafrate, Daniel Lingwood, Gaurav D. Gaiha, Richelle C. Charles, Alejandro B. Balazs, Aridaman Pandit, Vivek Naranbhai, Aaaron G Schmidt, Shiv Pillai
Abstract
Memory lymphocytes are durable cells that persist in the absence of antigen, but few human B cell subsets have been characterized in terms of durability. The relative durability of eight non-overlapping human B cell sub-populations covering 100% of all human class-switched B cells was interrogated. Only two long-lived B cell populations persisted in the relative absence of antigen. In addition to canonical germinal center-derived switched-memory B cells with an IgD − CD27 + CXCR5 + phenotype, a second, non-canonical, but distinct memory population of IgD − CD27 − CXCR5 + DN1 B cells was also durable, exhibited a unique TP63 -linked transcriptional and anti-apoptotic signature, had low levels of somatic hypermutation, but was more clonally expanded than canonical switched-memory B cells. DN1 B cells likely evolved to preserve immunological breadth and may represent the human counterparts of rodent extrafollicular memory B cells that, unlike canonical memory B cells, can enter germinal centers and facilitate B cell and antibody evolution.