Differential regulation of self-reactivity discriminates between IgG + human circulating memory B cells and bone marrow plasma cells
| Autor: | Hugo Mouquet, Michel C. Nussenzweig, Sergey Yurasov, Juliane Kofer, Hedda Wardemann, Johannes F. Scheid |
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| Rok vydání: | 2011 |
| Předmět: |
B-Lymphocytes
Multidisciplinary biology Somatic cell Plasma Cells Naive B cell Bone Marrow Cells Enzyme-Linked Immunosorbent Assay Biological Sciences Plasma cell Polymerase Chain Reaction Molecular biology Immunoglobulin G B-1 cell medicine.anatomical_structure Immunology Humoral immunity biology.protein medicine Humans Bone marrow Antibody Immunologic Memory |
| Zdroj: | Proceedings of the National Academy of Sciences. 108:18044-18048 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1113395108 |
| Popis: | Long-term humoral immunity is maintained by the formation of high-affinity class-switched memory B cells and long-lived antibody-secreting plasma cells. In healthy humans, a substantial fraction of IgG-positive memory B cells express self-reactive and polyreactive IgG antibodies that frequently develop by somatic mutations. Whether self- and polyreactive IgG-secreting B cells are also tolerated in the long-lived plasma cell pool is not known. To address this question, we cloned and expressed the Ig genes from 177 IgG-producing bone marrow plasma cells of four healthy donors. All antibodies were highly mutated but the frequency of self- and polyreactive IgG antibodies was significantly lower than that found in circulating memory B cells. The data suggest that in contrast to the development of memory B cells, entry into the bone marrow plasma cell compartment requires previously unappreciated selective regulation by mechanisms that limit the production of self- and polyreactive serum IgG antibodies. |
| Databáze: | OpenAIRE |
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