CD200R1 Marks a Branchpoint During Human Natural Killer Cell Development in Tonsils

Abstract

Human natural killer (NK) cells arise from common innate lymphoid cell (ILC) progenitor and precursor populations that are selectively enriched within secondary lymphoid tissues (SLTs) and that complete their terminal differentiation through stages of progressively lineage-restricted downstream developmental intermediates. We identify two subsets of tonsil CD94/NKG2A+NKp80- (stage 4A) NK-cell development intermediates that show differential expression of the inhibitory receptor, CD200R1. Ex vivo single-cell transcriptomic, DNA methylation, phenotypic, and functional analyses demonstrate that CD200R1 stage 4A cells represent an immature, oligopotent precursor population enriched for tissue-resident and cytokine-responsive programs. In contrast, CD200R1- stage 4A cells show more restricted NK-cell developmental potential concomitant with features of mature NK cells. These findings help to refine the human NK cell developmental pathway in tonsils and highlight CD200R1 as a useful marker delineating an uncommitted developmental state linking microenvironmental cues to NK-cell maturation and plasticity.

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BibTeX

@misc{youssef2026cd200r1,
  title = {{CD200R1 Marks a Branchpoint During Human Natural Killer Cell Development in Tonsils}},
  author = {Y. Youssef and A. Nalin and M. Ruesch and M. Lordo and N. T. Koenigs and D. Clever and J. Cesar and M. Broughton and W. K. Chan and A. G. Mansour and E. Altynova and X. Zhang and J. Blachly and B. Blaser and C. C. Oakes and B. L. Mundy-Bosse and b. kraemer and A. Freud},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.02.762613},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.02.762613v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - CD200R1 Marks a Branchpoint During Human Natural Killer Cell Development in Tonsils
AU  - Y. Youssef
AU  - A. Nalin
AU  - M. Ruesch
AU  - M. Lordo
AU  - N. T. Koenigs
AU  - D. Clever
AU  - J. Cesar
AU  - M. Broughton
AU  - W. K. Chan
AU  - A. G. Mansour
AU  - E. Altynova
AU  - X. Zhang
AU  - J. Blachly
AU  - B. Blaser
AU  - C. C. Oakes
AU  - B. L. Mundy-Bosse
AU  - b. kraemer
AU  - A. Freud
PY  - 2026
DA  - 2026/11/02
PB  - bioRxiv
DO  - 10.64898/2026.11.02.762613
UR  - https://www.biorxiv.org/content/10.64898/2026.11.02.762613v1
AB  - Human natural killer (NK) cells arise from common innate lymphoid cell (ILC) progenitor and precursor populations that are selectively enriched within secondary lymphoid tissues (SLTs) and that complete their terminal differentiation through stages of progressively lineage-restricted downstream developmental intermediates. We identify two subsets of tonsil CD94/NKG2A+NKp80- (stage 4A) NK-cell development intermediates that show differential expression of the inhibitory receptor, CD200R1. Ex vivo single-cell transcriptomic, DNA methylation, phenotypic, and functional analyses demonstrate that CD200R1 stage 4A cells represent an immature, oligopotent precursor population enriched for tissue-resident and cytokine-responsive programs. In contrast, CD200R1- stage 4A cells show more restricted NK-cell developmental potential concomitant with features of mature NK cells. These findings help to refine the human NK cell developmental pathway in tonsils and highlight CD200R1 as a useful marker delineating an uncommitted developmental state linking microenvironmental cues to NK-cell maturation and plasticity.
ER  -

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