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Peer-reviewedCC BY 4.0Nature Communications

Multi-omics profiling of primary human B cells activated via distinct stimuli

28 more authors

Abstract

B cells are central for immunity and immune-mediated diseases (IMD), but how distinct signaling pathways drive diverse activation responses over time is not comprehensively understood. Here, we obtain peripheral blood B cells from 27 female healthy donors for in vitro stimulation, profiling the response at multiple time points using RNA-seq, single-cell RNA-seq with surface protein markers (CITE-seq), and ATAC-seq. Using diverse stimuli including activation of the B cell receptor (BCR), Toll-like receptor 7 (TLR7), TLR9, CD40, and differentiation into double negative 2 (DN2) IgD – CD27 – CD11c ⁺ CD21 – B cells, our analyses uncover activation-dependent B cell states, stimulation-specific transcription factors and regulatory regions, the dynamic response of IMD-associated gene expression, and specific open chromatin regions associated with IMD genetic risk. Furthermore, we also identify a lupus risk variant in an enhancer regulating TNFSF4 expression. The analysis data can be accessed via an interactive browser: https://mgalab.shinyapps.io/bcellactivation . Our findings underscore how profiling the full breadth of B cell activation pathways may be important for understanding B cell biology in health and disease.

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BibTeX
@article{aguiar2026multiomics,
  title = {{Multi-omics profiling of primary human B cells activated via distinct stimuli}},
  author = {Vitor R. C. Aguiar and Marcella E. Franco and Nada Abdel Aziz and Daniela Fernandez-Salinas and Marcos Chiñas and Mariasilvia Colantuoni and Qian Xiao and Nicolaj Hackert and Yifei Liao and Rodrigo Cervantes-Diaz and Marc Todd and Brian Wauford and Alex Wactor and Vaishali Prahalad and Raquel Laza-Briviesca and Roxane Darbousset and Qiang Wang and Scott Jenks and Kevin S. Cashman and Esther Zumaquero and Zhu Zhu and Junning Case and Paloma Cejas and Miguel Gomez and Hannah Ainsworth and Miranda Marion and Mehdi Benamar and Pui Lee and Lauren Henderson and Margaret H. Chang and Kevin Wei and Henry Long and Carl D. Langefeld and Ashley D. Sanders and Benjamin E. Gewurz and Ignacio Sanz and Jeffrey A. Sparks and Esra Meidan and Peter A. Nigrovic and Maria Gutierrez-Arcelus},
  journal = {Nature Communications},
  year = {2026},
  month = oct,
  doi = {10.1038/s41467-026-78656-w},
  url = {https://www.nature.com/articles/s41467-026-78656-w},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Multi-omics profiling of primary human B cells activated via distinct stimuli
AU  - Vitor R. C. Aguiar
AU  - Marcella E. Franco
AU  - Nada Abdel Aziz
AU  - Daniela Fernandez-Salinas
AU  - Marcos Chiñas
AU  - Mariasilvia Colantuoni
AU  - Qian Xiao
AU  - Nicolaj Hackert
AU  - Yifei Liao
AU  - Rodrigo Cervantes-Diaz
AU  - Marc Todd
AU  - Brian Wauford
AU  - Alex Wactor
AU  - Vaishali Prahalad
AU  - Raquel Laza-Briviesca
AU  - Roxane Darbousset
AU  - Qiang Wang
AU  - Scott Jenks
AU  - Kevin S. Cashman
AU  - Esther Zumaquero
AU  - Zhu Zhu
AU  - Junning Case
AU  - Paloma Cejas
AU  - Miguel Gomez
AU  - Hannah Ainsworth
AU  - Miranda Marion
AU  - Mehdi Benamar
AU  - Pui Lee
AU  - Lauren Henderson
AU  - Margaret H. Chang
AU  - Kevin Wei
AU  - Henry Long
AU  - Carl D. Langefeld
AU  - Ashley D. Sanders
AU  - Benjamin E. Gewurz
AU  - Ignacio Sanz
AU  - Jeffrey A. Sparks
AU  - Esra Meidan
AU  - Peter A. Nigrovic
AU  - Maria Gutierrez-Arcelus
PY  - 2026
DA  - 2026/10/23
JO  - Nature Communications
DO  - 10.1038/s41467-026-78656-w
UR  - https://www.nature.com/articles/s41467-026-78656-w
AB  - B cells are central for immunity and immune-mediated diseases (IMD), but how distinct signaling pathways drive diverse activation responses over time is not comprehensively understood. Here, we obtain peripheral blood B cells from 27 female healthy donors for in vitro stimulation, profiling the response at multiple time points using RNA-seq, single-cell RNA-seq with surface protein markers (CITE-seq), and ATAC-seq. Using diverse stimuli including activation of the B cell receptor (BCR), Toll-like receptor 7 (TLR7), TLR9, CD40, and differentiation into double negative 2 (DN2) IgD – CD27 – CD11c ⁺ CD21 – B cells, our analyses uncover activation-dependent B cell states, stimulation-specific transcription factors and regulatory regions, the dynamic response of IMD-associated gene expression, and specific open chromatin regions associated with IMD genetic risk. Furthermore, we also identify a lupus risk variant in an enhancer regulating TNFSF4 expression. The analysis data can be accessed via an interactive browser: https://mgalab.shinyapps.io/bcellactivation . Our findings underscore how profiling the full breadth of B cell activation pathways may be important for understanding B cell biology in health and disease.
SN  - 2041-1723
ER  -