Academic Journal
CLL stereotyped B-cell receptor immunoglobulin sequences are recurrent in the B-cell repertoire of healthy individuals: Apparent lack of central and early peripheral tolerance censoring
| العنوان: | CLL stereotyped B-cell receptor immunoglobulin sequences are recurrent in the B-cell repertoire of healthy individuals: Apparent lack of central and early peripheral tolerance censoring |
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| المؤلفون: | Vergani S., Bagnara D., Agathangelidis A., Ng A. K. Y., Ferrer G., Mazzarello A. N., Palacios F., Yancopoulos S., Yan X. -J., Barrientos J. C., Rai K. R., Stamatopoulos K., Chiorazzi N. |
| المساهمون: | Vergani, S., Bagnara, D., Agathangelidis, A., Ng, A. K. Y., Ferrer, G., Mazzarello, A. N., Palacios, F., Yancopoulos, S., Yan, X. -J., Barrientos, J. C., Rai, K. R., Stamatopoulos, K., Chiorazzi, N. |
| بيانات النشر: | FRONTIERS MEDIA SA AVENUE DU TRIBUNAL FEDERAL 34, LAUSANNE, CH-1015, SWITZERLAND |
| سنة النشر: | 2023 |
| المجموعة: | Università degli Studi di Genova: CINECA IRIS |
| مصطلحات موضوعية: | B cell development and differentiation, B cell repertoire, CLL (chronic lymphocytic leukemia), VDJ sequencing, stereotyped antigen receptors |
| الوصف: | Introduction: The leukemic cells of patients with chronic lymphocytic leukemia (CLL) are often unique, expressing remarkably similar IGHV-IGHD-IGHJ gene rearrangements, "stereotyped BCRs". The B-cell receptors (BCRs) on CLL cells are also distinctive in often deriving from autoreactive B lymphocytes, leading to the assumption of a defect in immune tolerance.Results: Using bulk and single-cell immunoglobulin heavy and light chain variable domain sequencing, we enumerated CLL stereotype-like IGHV-IGHD-IGHJ sequences (CLL-SLS) in B cells from cord blood (CB) and adult peripheral blood (PBMC) and bone marrow (BM of healthy donors. CLL-SLS were found at similar frequencies among CB, BM, and PBMC, suggesting that age does not influence CLL-SLS levels. Moreover, the frequencies of CLL-SLS did not differ among B lymphocytes in the BM at early stages of development, and only re-circulating marginal zone B cells contained significantly higher CLL-SLS frequencies than other mature B-cell subpopulations. Although we identified CLL-SLS corresponding to most of the CLL major stereotyped subsets, CLL-SLS frequencies did not correlate with those found in patients. Interestingly, in CB samples, half of the CLL-SLS identified were attributed to two IGHV-mutated subsets. We also found satellite CLL-SLS among the same normal samples, and they were also enriched in naive B cells but unexpectedly, these were similar to 10-fold higher than standard CLL-SLS. In general, IGHV-mutated CLL-SLS subsets were enriched among antigen-experienced B-cell subpopulations, and IGHV-unmutated CLL-SLS were found mostly in antigen-inexperienced B cells. Nevertheless, CLL-SLS with an IGHV-mutation status matching that of CLL clones varied among the normal B-cell subpopulations, suggesting that specific CLL-SLS could originate from distinct subpopulations of normal B cells. Lastly, using single-cell DNA sequencing, we identified paired IGH and IGL rearrangements in normal B lymphocytes resembling those of stereotyped BCRs in CLL, although some differed ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | ELETTRONICO |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/37007084; info:eu-repo/semantics/altIdentifier/wos/WOS:000961536700001; volume:13; firstpage:1112879; lastpage:1112879; numberofpages:1; journal:FRONTIERS IN ONCOLOGY; info:eu-repo/grantAgreement/EC/H2020/101023721; https://hdl.handle.net/11567/1117815; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85152377120 |
| DOI: | 10.3389/fonc.2023.1112879 |
| الاتاحة: | https://hdl.handle.net/11567/1117815 https://doi.org/10.3389/fonc.2023.1112879 |
| رقم الانضمام: | edsbas.F8E12E5B |
| قاعدة البيانات: | BASE |
| DOI: | 10.3389/fonc.2023.1112879 |
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