Expansion of Polyreactive B Cells Cross-Reactive to HLA and Self in the Blood of a Patient With Kidney Graft Rejection
| Autor: | Waichi Wong, Christian LeGuern, Jack Ferdman, Timothy C. Girouard, Tatsuo Kawai, Susan L. Saidman, Priscilla Nobecourt, James W. Fraser, Julie DeVito, Robert B. Colvin, Ynes Helou, Ian Dargon, Sharon Germana, Fabrice Porcheray, Emmanuel Zorn |
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| Rok vydání: | 2012 |
| Předmět: |
Graft Rejection
Somatic cell Clone (cell biology) Fluorescent Antibody Technique Human leukocyte antigen Cross Reactions Article HLA Antigens medicine Humans Immunology and Allergy Pharmacology (medical) Kidney transplantation B-Lymphocytes Transplantation Kidney biology Autoantibody medicine.disease Kidney Transplantation Phenotype Molecular biology medicine.anatomical_structure Immunology biology.protein Antibody |
| Zdroj: | American Journal of Transplantation |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/j.1600-6143.2012.04053.x |
| Popis: | Antibody rejection is often accompanied by nondonor HLA specific antibodies (NDSA) and self-reactive antibodies that develop alongside donor-specific antibodies (DSA). To determine the source of these antibodies, we immortalized 107 B-cell clones from a kidney transplant recipient with humoral rejection. Two of these clones reacted to HLA class I or MICA. Both clones were also reactive to self-antigens and a lysate of a kidney cell line, hence revealing a pattern of polyreactivity. Monoclonality was verified by the identification of a single rearranged immunoglobulin heavy chain variable region (VH) sequence for each clone. By tracking their unique CDR3 sequence, we found that one such polyreactive clone was highly expanded in the patient blood, representing ~0.2% of circulating B cells. The VH sequence of this clone showed evidence of somatic mutations that were consistent with its memory phenotype and its expansion. Lastly, the reactivity of the expanded polyreactive B-cell clone was found in the patient serum at time of rejection. In conclusion, we provide here proof of principle at the clonal level that human antibodies can cross-react to HLA and self. Our findings strongly suggest that polyreactive antibodies contribute to DSA, NDSA as well as autoantibodies, in transplant recipients. |
| Databáze: | OpenAIRE |
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