دورية أكاديمية
Phenotypic determinism and stochasticity in antibody repertoires of clonally expanded plasma cells.
| العنوان: | Phenotypic determinism and stochasticity in antibody repertoires of clonally expanded plasma cells. |
|---|---|
| المؤلفون: | Neumeier D; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Yermanos A; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.; Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland.; Department of Pathology and Immunology, University of Geneva, 1205 Geneva, Switzerland., Agrafiotis A; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.; Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland., Csepregi L; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Chowdhury T; UCB Pharma, Slough SL1 3WE, United Kingdom., Ehling RA; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Kuhn R; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Cotet TS; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Brisset-Di Roberto R; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Di Tacchio M; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Antonialli R; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland., Starkie D; UCB Pharma, Slough SL1 3WE, United Kingdom., Lightwood DJ; UCB Pharma, Slough SL1 3WE, United Kingdom., Oxenius A; Institute of Microbiology, ETH Zürich, 8093 Zurich, Switzerland., Reddy ST; Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland. |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 May 03; Vol. 119 (18), pp. e2113766119. Date of Electronic Publication: 2022 Apr 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Antigens* , Plasma Cells*, Animals ; Antibodies/genetics ; Antibody Affinity ; Epitopes/genetics ; Mice |
| مستخلص: | The capacity of humoral B cell-mediated immunity to effectively respond to and protect against pathogenic infections is largely driven by the presence of a diverse repertoire of polyclonal antibodies in the serum, which are produced by plasma cells (PCs). Recent studies have started to reveal the balance between deterministic mechanisms and stochasticity of antibody repertoires on a genotypic level (i.e., clonal diversity, somatic hypermutation, and germline gene usage). However, it remains unclear if clonal selection and expansion of PCs follow any deterministic rules or are stochastic with regards to phenotypic antibody properties (i.e., antigen-binding, affinity, and epitope specificity). Here, we report on the in-depth genotypic and phenotypic characterization of clonally expanded PC antibody repertoires following protein immunization. We find that clonal expansion drives antigen specificity of the most expanded clones (top ∼10), whereas among the rest of the clonal repertoire antigen specificity is stochastic. Furthermore, we report both on a polyclonal repertoire and clonal lineage level that antibody-antigen binding affinity does not correlate with clonal expansion or somatic hypermutation. Last, we provide evidence for convergence toward targeting dominant epitopes despite clonal sequence diversity among the most expanded clones. Our results highlight the extent to which clonal expansion can be ascribed to antigen binding, affinity, and epitope specificity, and they have implications for the assessment of effective vaccines. |
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| فهرسة مساهمة: | Keywords: antibody; epitope; repertoire; sequencing; specificity |
| المشرفين على المادة: | 0 (Antibodies) 0 (Antigens) 0 (Epitopes) |
| تواريخ الأحداث: | Date Created: 20220429 Date Completed: 20220503 Latest Revision: 20220716 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9170022 |
| DOI: | 10.1073/pnas.2113766119 |
| PMID: | 35486691 |
| قاعدة البيانات: | MEDLINE |
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