Peer-reviewedCC BY 4.0Nature immunology
Spatial confinement promotes germinal center diversity and tempers immunodominance
12 affiliations
- 1Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA 94143, USA
- 2Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
- 3Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
- 4Department of Systems Immunology, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany.
- 5Department of Gastroenterology, University of California San Francisco, San Francisco, CA 94143, USA
- 6Université de Reims Champagne-Ardenne, INSERM, P3Cell UMR-S1250, SFR CAP-SANTE, Reims 51097, France
- 7Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712 USA
- 8Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02215, USA
- 9The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA
- 10Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany
- 11Lower Saxony Center for Artificial Intelligence and Causal Methods in Medicine (CAIMed), Hannover, Germany.
- 12Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94304, USA
Abstract
Germinal centers (GCs) form as confined clusters of motile cells within individual lymphoid follicles. The role of confinement in GC B cell evolutionary events is unknown. Using mice with reduced GC confinement due to deficiency in Gα13-dependent G-protein-coupled receptor signaling, we observed GC-to-GC trafficking in confinement-defective lymph nodes (LNs). In multi-color clonal lineage tracing mice, de-confined GCs minimally diversified their color palettes with respect to one another. Spatial B cell receptor sequencing revealed greater clonal crossover between neighboring GCs in the setting of dispersal. The total GC B cell repertoire of LNs with inter-GC exchange also decreased in overall diversity due to increased skewing towards top clones. As an outcome, LNs with de-confined GCs more strongly favored clones responding to accessible epitopes while losing clones binding to other portions of antigen. Together, our findings suggest that confinement supports antibody breadth by moderating the spread of dominant clones and preserving unique trajectories in individual GC responses.
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BibTeX
@article{chen2026spatial,
title = {{Spatial confinement promotes germinal center diversity and tempers immunodominance}},
author = {Kevin Y. Chen and Kenneth H. Hu and Nikhita Kirthivasan and Anshul Rao and Niklas Schwan and Jinping An and Ying Xu and Vincent Peng and Mélia Magnen and Sijin Huang and Qian Yin and Debraj Ghose and Caroline Alexander and Jack Smerczynski and Michael Meyer-Hermann and Matthew F. Krummel and Vamsee Mallajosyula and Daniel Lingwood and Jason G. Cyster},
journal = {Nature immunology},
year = {2026},
month = oct,
doi = {10.1038/s41590-026-02698-x},
url = {https://doi.org/10.1038/s41590-026-02698-x},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Spatial confinement promotes germinal center diversity and tempers immunodominance
AU - Kevin Y. Chen
AU - Kenneth H. Hu
AU - Nikhita Kirthivasan
AU - Anshul Rao
AU - Niklas Schwan
AU - Jinping An
AU - Ying Xu
AU - Vincent Peng
AU - Mélia Magnen
AU - Sijin Huang
AU - Qian Yin
AU - Debraj Ghose
AU - Caroline Alexander
AU - Jack Smerczynski
AU - Michael Meyer-Hermann
AU - Matthew F. Krummel
AU - Vamsee Mallajosyula
AU - Daniel Lingwood
AU - Jason G. Cyster
PY - 2026
DA - 2026/10/21
JO - Nature immunology
DO - 10.1038/s41590-026-02698-x
UR - https://doi.org/10.1038/s41590-026-02698-x
AB - Germinal centers (GCs) form as confined clusters of motile cells within individual lymphoid follicles. The role of confinement in GC B cell evolutionary events is unknown. Using mice with reduced GC confinement due to deficiency in Gα13-dependent G-protein-coupled receptor signaling, we observed GC-to-GC trafficking in confinement-defective lymph nodes (LNs). In multi-color clonal lineage tracing mice, de-confined GCs minimally diversified their color palettes with respect to one another. Spatial B cell receptor sequencing revealed greater clonal crossover between neighboring GCs in the setting of dispersal. The total GC B cell repertoire of LNs with inter-GC exchange also decreased in overall diversity due to increased skewing towards top clones. As an outcome, LNs with de-confined GCs more strongly favored clones responding to accessible epitopes while losing clones binding to other portions of antigen. Together, our findings suggest that confinement supports antibody breadth by moderating the spread of dominant clones and preserving unique trajectories in individual GC responses.
SN - 1529-2908
SN - 1529-2916
ER -