Two distinct durable human class-switched memory B cell populations are induced by vaccination and infection
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<sup>-</sup>CD27<sup>+</sup>CXCR5<sup>+</sup> phenotype, a second, non-canonical, but distinct memory population of IgD<sup>-</sup>CD27<sup>-</sup>CXCR5<sup>+</sup> 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.
Authors
- Gaurav D. Gaiha (ORCID: https://orcid.org/0000-0001-6875-4472)
- Zachary Manickas-Hill (ORCID: https://orcid.org/0000-0002-9880-2356)
- Marcia B. Goldberg (ORCID: https://orcid.org/0000-0003-4266-9733)
- Weiyang Tao (ORCID: https://orcid.org/0000-0003-0011-6516)
- Neha Chaudhary (ORCID: https://orcid.org/0000-0003-3510-1322)
- Richelle C. Charles (ORCID: https://orcid.org/0000-0002-8881-1849)
- Onosereme Ofoman
- John Iafrate
- Matthew A. Getz (ORCID: https://orcid.org/0000-0002-4172-2187)
- Cory A. Perugino
- Jacob E. Lemieux (ORCID: https://orcid.org/0000-0002-2758-4005)
- Duane R. Wesemann (ORCID: https://orcid.org/0000-0002-6690-944X)
- Jared Feldman (ORCID: https://orcid.org/0000-0002-4387-9954)
- Edward Thomas Ryan (ORCID: https://orcid.org/0009-0005-0169-394X)
- Blake M. Hauser (ORCID: https://orcid.org/0000-0002-0100-1684)
- Regina C. LaRocque (ORCID: https://orcid.org/0000-0003-4558-0339)
- Zezhou Zhao (ORCID: https://orcid.org/0000-0003-4792-6073)
- Anusha Nathan (ORCID: https://orcid.org/0000-0002-4418-1005)
- Catherine Jacob-Dolan (ORCID: https://orcid.org/0000-0001-6641-0342)
- Aaaron G Schmidt
- Clarety Kaseke (ORCID: https://orcid.org/0000-0001-9293-6508)
- Alejandro B. Balazs (ORCID: https://orcid.org/0000-0002-1767-3944)
- Shiv Pillai (ORCID: https://orcid.org/0000-0002-9905-875X)
- Ann M. Moormann (ORCID: https://orcid.org/0000-0003-1113-2829)
- Cristhian Berrios
- Vivek Naranbhai (ORCID: https://orcid.org/0000-0003-4281-8882)
- Rhoda Tano-Menka
- Ann Marshak‐Rothstein (ORCID: https://orcid.org/0000-0003-2136-8130)
- Fernando Senjobe (ORCID: https://orcid.org/0000-0003-4322-6571)
- Kerstin Nündel (ORCID: https://orcid.org/0000-0003-4329-9607)
- Hang Liu (ORCID: https://orcid.org/0000-0002-7352-7407)
- Daniel Lingwood (ORCID: https://orcid.org/0000-0003-0374-1982)
- Thomas V. Guy (ORCID: https://orcid.org/0009-0009-0383-4469)
- Zayd Mian
- Aridaman Pandit
- Jess Marbourg
- Anson Hui
- Nicole Ingram
- Julian Liebaert
Institutions
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- University of Massachusetts Chan Medical School (US)
- Centre for the AIDS Programme of Research in South Africa (ZA)
- Ragon Institute of MGH, MIT and Harvard (US)
- AbbVie (United States) (US)
- Massachusetts General Hospital (US)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115472
- Citations
- 8
- Primary Topic
- T-cell and B-cell Immunology
- Type
- article
- Field-Weighted Citation Impact
- 6.38