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Peer-reviewedCC BY 4.0The EMBO Journal

Expression patterns of CD24 and CD27 resolve the origins and gradual differentiation of CD11c+ atypical memory B-cells after malaria infection

  • Alan-Dine Courey-Ghaouzi1,2,3
  • Linn Kleberg1,2,3
  • Zaynab Mousavian1,2,3,4
  • Maximilian Julius Lautenbach1,2,3
  • Marta Pirronello5
  • Ganesh E Phad6
  • Mattias N E Forsell7
  • Anna Färnert1,2,3
  • Christopher Sundling1,2,3
7 affiliations
  1. 1Division of Infectious Diseases, Department of Medicine, Karolinska Institutet, Solna, Sweden
  2. 2Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden
  3. 3Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden
  4. 4Hubert Department of Global Health, Emory University Rollins School of Public Health, Atlanta, GA USA
  5. 5Neuroimmunology Unit, Santa Lucia Foundation IRCCS, Rome, Italy
  6. 6Christine Kühne – Center for Allergy Research and Education (CK-CARE), Davos, Switzerland
  7. 7Department of Clinical Microbiology, Umeå University, Umeå, Sweden
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Abstract

Atypical B-cells (ABCs) are observed across infections, yet their ontogeny and differentiation remain unclear. Using high-dimensional flow cytometry, single-cell transcriptomics, V(D)J sequencing, and functional assays in samples from individuals with malaria and healthy donors, we identify markers of cellular origin while tracking ABC differentiation. Early ABCs express CD11c and arise predominantly from memory B-cells. Two intermediate states originate from germinal center-derived and marginal zone-like B-cells. Pseudotime and lineage analyses reveal trajectories marked by progressive loss of CD24 and CD27, which is recapitulated in vitro, defining bona fide differentiation programs. Differentiation culminates in late ABCs lacking CD24, CD27, and CD21, while expressing CD11c, T-bet, and NKG7 at high levels, exhibiting partial overlap with double-negative-2 B-cells. Early and intermediate stages show greater plasma-cell differentiation potential and cytokine production capacity, whereas later stages acquire transcriptomic signatures of antigen presentation and association with microbial particles, defining stage-dependent functions that reconcile conflicting ABC roles. Comparable ABC populations occur in healthy blood and tonsils, with tissue-associated class switching and CD86 expression consistent with recent T-cell interaction. This framework consolidates ABC definitions along a single differentiation axis and clarifies their cellular origins.

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Cite

BibTeXRIS
BibTeX
@article{coureyghaouzi2026expression,
  title = {{Expression patterns of CD24 and CD27 resolve the origins and gradual differentiation of CD11c+ atypical memory B-cells after malaria infection}},
  author = {Alan-Dine Courey-Ghaouzi and Linn Kleberg and Zaynab Mousavian and Maximilian Julius Lautenbach and Marta Pirronello and Ganesh E Phad and Mattias N E Forsell and Anna Färnert and Christopher Sundling},
  journal = {The EMBO Journal},
  year = {2026},
  month = oct,
  doi = {10.1038/s44318-026-00941-7},
  url = {https://doi.org/10.1038/s44318-026-00941-7},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Expression patterns of CD24 and CD27 resolve the origins and gradual differentiation of CD11c+ atypical memory B-cells after malaria infection
AU  - Alan-Dine Courey-Ghaouzi
AU  - Linn Kleberg
AU  - Zaynab Mousavian
AU  - Maximilian Julius Lautenbach
AU  - Marta Pirronello
AU  - Ganesh E Phad
AU  - Mattias N E Forsell
AU  - Anna Färnert
AU  - Christopher Sundling
PY  - 2026
DA  - 2026/10/11
JO  - The EMBO Journal
DO  - 10.1038/s44318-026-00941-7
UR  - https://doi.org/10.1038/s44318-026-00941-7
AB  - Atypical B-cells (ABCs) are observed across infections, yet their ontogeny and differentiation remain unclear. Using high-dimensional flow cytometry, single-cell transcriptomics, V(D)J sequencing, and functional assays in samples from individuals with malaria and healthy donors, we identify markers of cellular origin while tracking ABC differentiation. Early ABCs express CD11c and arise predominantly from memory B-cells. Two intermediate states originate from germinal center-derived and marginal zone-like B-cells. Pseudotime and lineage analyses reveal trajectories marked by progressive loss of CD24 and CD27, which is recapitulated in vitro, defining bona fide differentiation programs. Differentiation culminates in late ABCs lacking CD24, CD27, and CD21, while expressing CD11c, T-bet, and NKG7 at high levels, exhibiting partial overlap with double-negative-2 B-cells. Early and intermediate stages show greater plasma-cell differentiation potential and cytokine production capacity, whereas later stages acquire transcriptomic signatures of antigen presentation and association with microbial particles, defining stage-dependent functions that reconcile conflicting ABC roles. Comparable ABC populations occur in healthy blood and tonsils, with tissue-associated class switching and CD86 expression consistent with recent T-cell interaction. This framework consolidates ABC definitions along a single differentiation axis and clarifies their cellular origins.
SN  - 0261-4189
SN  - 1460-2075
ER  -