{ "abstract": "The adaptive immune system recognizes billions of unique antigens using highly variable T cell receptors (TCRs). To what extent TCR features shape the spatial distribution of the TCR repertoire (TCR-R) within lymphoid organs remains unclear. Here, we compared the TCR-R composition in T cell zones (TCZ), B cell zones (BCZ), and germinal centers (GC) of the spleen by analyzing the complementarity-determining region 3 of the beta chain (CDR3β) in microdissected splenic compartments from naïve and immunized mice. While we found substantial differences in TCR-R composition between these compartments, these differences largely disappeared once the effects of compartment size and proliferation were accounted for: During steady state, the few T cells found in BCZs strongly resemble random subsets of those found in TCZs. After immunization, expanded clones started appearing in the TCZ at day 3 and later shifted to the BCZ. GCs harbored even further expanded clones that were grouped into clusters with high sequence similarity. TCR-R differences during the immune response were well explained by a Galton-Watson model of T cell proliferation, suggesting that this could be the central factor shaping the observed TCR-R differences. Similarly, while TCR length and closeness to germline initially showed more pronounced differences between the compartments, our models of random distribution and proliferation explained these differences almost entirely. Hence, our findings suggest that splenic TCR-Rs are shaped predominantly by compartment size and proliferation rates rather than TCR sequence features. This would imply that quantitative assessment of TCR-R dynamics across heterogeneous spatial compartments during an immune response is only possible when these effects are explicitly accounted for. Author summary: T cells are an integral part of the adaptive immune system, working with B cells to detect and remove infectious and cancerous cells. To do this, they have receptors that recognize small peptides (antigens) presented by other cells. The immune system has a large repertoire of T cell receptors (TCRs). During an immune response, cells that recognize an antigen expand.", "abstract_shown": true, "affiliations": [ "Data Science Group, Institute for Computing and Information Sciences, Radboud University, Nijmegen, The Netherlands.", "Institut für Anatomie, Universität zu Lübeck, Lübeck, Germany.", "Medical BioSciences, Radboud University Medical Center, Nijmegen, The Netherlands." ], "article_type": "Research Article", "arxiv": null, "author_total": 8, "authors": [ { "affs": [ 0 ], "name": "Franka Buytenhuijs" }, { "affs": [ 1 ], "name": "Cornelia Tune" }, { "affs": [ 2 ], "name": "Thomas C Smits" }, { "affs": [ 1 ], "name": "Andrea Schampel" }, { "affs": [ 1 ], "name": "Lisa-Kristin Schierloh" }, { "affs": [ 1 ], "name": "René Pagel" }, { "affs": [ 1 ], "name": "Jürgen Westermann" }, { "affs": [ 0, 2 ], "name": "Johannes Textor", "orcid": "0000-0002-0459-9458" } ], "bibtex": "https://research.draconitic.com/paper/aw0spe61qhfqd.bib", "cited_by": 0, "doi": "10.1371/journal.pcbi.1014859", "fulltext_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014859", "id": "aw0spe61qhfqd", "issns": [ "1553-7358", "1553-734X" ], "landing_url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014859", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2403|T-cell and B-cell Immunology" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/Immune system proteins/Immune receptors/T cell receptors" ], [ "plos", "/Biology and life sciences/Biochemistry/Proteins/T cell receptors" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/B cells" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/Antibody-producing cells/B cells" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/B cells" ], [ "plos", "/Biology and life sciences/Cell biology/Signal transduction/Immune receptors/T cell receptors" ], [ "plos", "/Biology and life sciences/Immunology/Antigen processing and recognition" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/Antibody-producing cells/B cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/B cells" ], [ "plos", "/Biology and life sciences/Immunology/Immune response" ], [ "plos", "/Biology and life sciences/Immunology/Immune system proteins/Immune receptors/T cell receptors" ], [ "plos", "/Biology and life sciences/Molecular biology/Molecular biology techniques/Cloning" ], [ "plos", "/Biology and life sciences/Molecular biology/Molecular biology techniques/Sequencing techniques/Protein sequencing" ], [ "plos", "/Biology and life sciences/Physiology/Immune physiology/Spleen" ], [ "plos", "/Medicine and health sciences/Immunology/Antigen processing and recognition" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/Antibody-producing cells/B cells" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/B cells" ], [ "plos", "/Medicine and health sciences/Immunology/Immune response" ], [ "plos", "/Medicine and health sciences/Immunology/Immune system proteins/Immune receptors/T cell receptors" ], [ "plos", "/Research and analysis methods/Molecular biology techniques/Cloning" ], [ "plos", "/Research and analysis methods/Molecular biology techniques/Sequencing techniques/Protein sequencing" ], [ "plos", "/Research and analysis methods/Specimen preparation and treatment/Staining/Cell staining" ] ], "openalex": "W7221814440", "pdf_url": "https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1014859&type=printable", "pmcid": "PMC13690269", "pmid": "42873830", "published": "2026-10-14", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/aw0spe61qhfqd.ris", "sources": [ { "first_seen": "2026-10-30T12:17:23Z", "native_id": "10.1371/journal.pcbi.1014859", "source": "plos", "url": "https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1014859" }, { "first_seen": "2026-10-30T12:18:46Z", "native_id": "MED:42873830", "source": "europepmc", "url": "https://europepmc.org/article/MED/42873830" } ], "subjects": [ { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" } ], "title": "How compartmentalization and proliferation shape the splenic T cell repertoire during an immune response to a complex antigen in mice", "title_text": "How compartmentalization and proliferation shape the splenic T cell repertoire during an immune response to a complex antigen in mice", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:46Z", "url": "https://research.draconitic.com/paper/aw0spe61qhfqd", "venue": "PLOS Computational Biology", "versions": [] }