The formation of mutated IgM memory B cells in rat splenic marginal zones is an antigen dependent process
| Autor: | Annie Visser, Jacobus Hendricks, Nicolaas A. Bos, Peter M. Dammers, Frans G. M. Kroese, Johannes G. M. Burgerhof |
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| Přispěvatelé: | Life Course Epidemiology (LCE), Translational Immunology Groningen (TRIGR), Lifelong Learning, Education & Assessment Research Network (LEARN) |
| Rok vydání: | 2019 |
| Předmět: |
Male
B Cells Physiology Somatic cell Immunoglobulin Variable Region medicine.disease_cause White Blood Cells 0302 clinical medicine Animal Cells Spleen/cytology Immune Physiology Medicine and Health Sciences Antigens/immunology Mammals B-Lymphocytes 0303 health sciences Mutation Multidisciplinary Database and informatics methods Sequence analysis Eukaryota B-Lymphocytes/immunology Animal Models Marginal zone medicine.anatomical_structure Experimental Organism Systems Vertebrates Medicine Cellular Types IGHV@ Research Article Bioinformatics Immune Cells Science Immunology Spleen Biology Rodents Immunoglobulin M/genetics 03 medical and health sciences Model Organisms Immune system Antigen Genetics medicine Animals Antigens Antibody-Producing Cells DNA sequence analysis Immunoglobulin Variable Region/genetics 030304 developmental biology Blood Cells Organisms Biology and Life Sciences Germinal center Cell Biology Memory B cells Molecular biology Rats Research and analysis methods Immunoglobulin M Amniotes Animal Studies Immunologic Memory 030215 immunology |
| Zdroj: | PLoS ONE, 14(9):e0220933. PUBLIC LIBRARY SCIENCE PLoS ONE, Vol 14, Iss 9, p e0220933 (2019) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0220933 |
| Popis: | Previous studies in rodents have indicated that only a minor fraction of the immunoglobulin heavy chain variable region (IGHV-Cμ) transcripts carry somatic mutations and are considered memory B cells. This is in marked contrast to humans where nearly all marginal zone B (MZ-B) cells are mutated. Here we show in rats that the proportion of mutated IgM+ MZ-B cells varies significantly between the various IGHV genes analyzed, ranging from 27% mutated IGHV5 transcripts to 65% mutated IGHV4 transcripts. The observed data on mutated sequences in clonally-related B cells with a MZ-B cell or follicular B (FO-B) cell phenotype indicates that mutated IgM+ MZ-B and FO-B cells have a common origin. To further investigate the origin of mutated IgM+ MZ-B cells we determined whether mutations occurred in rearranged IGHV-Cμ transcripts using IGHV4 and IGHV5 genes from neonatal rat MZ-B cells and FO-B cells. We were not able to detect mutations in any of the IGHV4 and IGHV5 genes expressed by MZ-B cells or FO-B cells obtained from neonatal rat spleens. Germinal centres (GCs) are absent from neonatal rat spleen in the first few weeks of their life, and no mutations were found in any of the neonatal sequences, not even in the IGHV4 gene family which accumulates the highest number of mutated sequences (66%) in the adult rat. Therefore, these data do not support the notion that MZ-B cells in rats mutate their IGHV genes as part of their developmental program, but are consistent with the notion that mutated rat MZ-B cells require GCs for their generation. Our findings support that the splenic MZ of rats harbors a significant number of memory type IgM+ MZ-B cells with mutated IGHV genes and propose that these memory MZ-B cells are probably generated as a result of an antigen driven immune response in GCs, which still remains to be proven. |
| Databáze: | OpenAIRE |
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