Class-Switch Recombination Occurs Infrequently in Germinal Centers
| Autor: | Kai-Michael Toellner, Michael Meyer-Hermann, Sebastian Binder, Jean Cappello, Harpreet Vohra, Julia I. Ellyard, Christian M. Nefzger, Jose M. Polo, Pablo F. Canete, Jonathan A. Roco, Luka Mesin, Carla R. Nowosad, Gabriel D. Victora, Ariën Schiepers, Paula Gonzalez-Figueroa, Philippe Robert, Qian Shen, Yang Zhang, Lynn M. Corcoran, Carola G. Vinuesa |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
History T cell Plasma Cells Immunology Receptors Antigen B-Cell Priming (immunology) Somatic hypermutation chemical and pharmacologic phenomena Biology Article Germline Education Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans Immunology and Allergy Cells Cultured Phylogeny B cell Physics B-Lymphocytes Germinal center Cell Differentiation T-Lymphocytes Helper-Inducer Germinal Center Immunoglobulin Class Switching Isotype Computer Science Applications Cell biology Mice Inbred C57BL 030104 developmental biology Infectious Diseases medicine.anatomical_structure Immunoglobulin class switching 030220 oncology & carcinogenesis Plasmablastic Lymphoma Recombination 030215 immunology |
| Zdroj: | Immunity |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2019.07.001 |
| Popis: | Class-switch recombination (CSR) is a DNA recombination process that replaces the immunoglobulin (Ig) constant region for the isotype that can best protect against the pathogen. Dysregulation of CSR can cause self-reactive BCRs and B cell lymphomas; understanding the timing and location of CSR is therefore important. Although CSR commences upon T cell priming, it is generally considered a hallmark of germinal centers (GCs). Here, we have used multiple approaches to show that CSR is triggered prior to differentiation into GC B cells or plasmablasts and is greatly diminished in GCs. Despite finding a small percentage of GC B cells expressing germline transcripts, phylogenetic trees of GC BCRs from secondary lymphoid organs revealed that the vast majority of CSR events occurred prior to the onset of somatic hypermutation. As such, we have demonstrated the existence of IgM-dominated GCs, which are unlikely to occur under the assumption of ongoing switching. |
| Databáze: | OpenAIRE |
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