Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements
Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of monoclonal CD5+ B cells with low surface immunoglobulins (IG). About 40% of CLL clones utilize quasi-identical B cell receptors, defined as stereotyped BCR. CLL-like stereotyped-IG rearrangements are present in normal B cells...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.894419/full |
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| author | Davide Bagnara Monica Colombo Daniele Reverberi Serena Matis Rosanna Massara Niccolò Cardente Gianluca Ubezio Vanessa Agostini Luca Agnelli Luca Agnelli Antonino Neri Martina Cardillo Stefano Vergani Fabio Ghiotto Fabio Ghiotto Andrea Nicola Mazzarello Fortunato Morabito Fortunato Morabito Giovanna Cutrona Manlio Ferrarini Franco Fais Franco Fais |
| author_facet | Davide Bagnara Monica Colombo Daniele Reverberi Serena Matis Rosanna Massara Niccolò Cardente Gianluca Ubezio Vanessa Agostini Luca Agnelli Luca Agnelli Antonino Neri Martina Cardillo Stefano Vergani Fabio Ghiotto Fabio Ghiotto Andrea Nicola Mazzarello Fortunato Morabito Fortunato Morabito Giovanna Cutrona Manlio Ferrarini Franco Fais Franco Fais |
| author_sort | Davide Bagnara |
| collection | DOAJ |
| description | Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of monoclonal CD5+ B cells with low surface immunoglobulins (IG). About 40% of CLL clones utilize quasi-identical B cell receptors, defined as stereotyped BCR. CLL-like stereotyped-IG rearrangements are present in normal B cells as a part of the public IG repertoire. In this study, we collected details on the representation and features of CLL-like stereotyped-IG in the IGH repertoire of B-cell subpopulations purified from the peripheral blood of nine healthy donors. The B-cell subpopulations were also fractioned according to the expression of surface CD5 molecules and IG light chain, IGκ and IGλ. IG rearrangements, obtained by high throughput sequencing, were scanned for the presence of CLL-like stereotyped-IG. CLL-like stereotyped-IG did not accumulate preferentially in the CD5+ B cells, nor in specific B-cell subpopulations or the CD5+ cell fraction thereof, and their distribution was not restricted to a single IG light chain type. CLL-like stereotyped-IG shared with the corresponding CLL stereotype rearrangements the IGHV mutational status. Instead, for other features such as IGHV genes and frequency, CLL stereotyped-IGs presented a CLL-like subset specific behavior which could, or could not, be consistent with CLL stereotyped-IGs. Therefore, as opposed to the immuno-phenotype, the features of the CLL stereotyped-IG repertoire suggest a CLL stereotyped subset-specific ontogeny. Overall, these findings suggest that the immune-genotype can provide essential details in tracking and defining the CLL cell of origin. |
| first_indexed | 2024-12-12T06:50:28Z |
| format | Article |
| id | doaj.art-dfe95720f8234d16aa1da46d4f7ef4f3 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-12T06:50:28Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-dfe95720f8234d16aa1da46d4f7ef4f32022-12-22T00:34:04ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.894419894419Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin RearrangementsDavide Bagnara0Monica Colombo1Daniele Reverberi2Serena Matis3Rosanna Massara4Niccolò Cardente5Gianluca Ubezio6Vanessa Agostini7Luca Agnelli8Luca Agnelli9Antonino Neri10Martina Cardillo11Stefano Vergani12Fabio Ghiotto13Fabio Ghiotto14Andrea Nicola Mazzarello15Fortunato Morabito16Fortunato Morabito17Giovanna Cutrona18Manlio Ferrarini19Franco Fais20Franco Fais21Department of Experimental Medicine, University of Genoa, Genoa, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyTransfusion Centre, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyTransfusion Centre, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Pathology, IRCCS Istituto Nazionale dei Tumori, Milan, ItalyDepartment of Oncology and Hemato-oncology, University of Milan, Milan, ItalyScientific Directorate, Azienza Unità Sanitaria Locale (USL)-IRCCS di Reggio Emilia, Reggio Emilia, ItalyKarches Center for Oncology Research, The Feinstein Institute for Medical Research, Manhasset, NY, United StatesDevelopmental Immunology Unit, Division of Molecular Hematology, Department of Laboratory Medicine, Lund Stem Cell Center, Lund University, Lund, SwedenDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyHematology and Bone Marrow Transplant Unit, Hemato-Oncology Department, Augusta Victoria Hospital, East Jerusalem, Israel0Biothecnology Research Unit, AO of Cosenza, Cosenza, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyDepartment of Experimental Medicine, University of Genoa, Genoa, ItalyMolecular Pathology, IRCCS Ospedale Policlinico San Martino, Genoa, ItalyChronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of monoclonal CD5+ B cells with low surface immunoglobulins (IG). About 40% of CLL clones utilize quasi-identical B cell receptors, defined as stereotyped BCR. CLL-like stereotyped-IG rearrangements are present in normal B cells as a part of the public IG repertoire. In this study, we collected details on the representation and features of CLL-like stereotyped-IG in the IGH repertoire of B-cell subpopulations purified from the peripheral blood of nine healthy donors. The B-cell subpopulations were also fractioned according to the expression of surface CD5 molecules and IG light chain, IGκ and IGλ. IG rearrangements, obtained by high throughput sequencing, were scanned for the presence of CLL-like stereotyped-IG. CLL-like stereotyped-IG did not accumulate preferentially in the CD5+ B cells, nor in specific B-cell subpopulations or the CD5+ cell fraction thereof, and their distribution was not restricted to a single IG light chain type. CLL-like stereotyped-IG shared with the corresponding CLL stereotype rearrangements the IGHV mutational status. Instead, for other features such as IGHV genes and frequency, CLL stereotyped-IGs presented a CLL-like subset specific behavior which could, or could not, be consistent with CLL stereotyped-IGs. Therefore, as opposed to the immuno-phenotype, the features of the CLL stereotyped-IG repertoire suggest a CLL stereotyped subset-specific ontogeny. Overall, these findings suggest that the immune-genotype can provide essential details in tracking and defining the CLL cell of origin.https://www.frontiersin.org/articles/10.3389/fonc.2022.894419/fullchronic lymphocytic leukemia (CLL)immunoglobulin repertoireB-cellsCD5IGHV somatic mutationsIg light chain |
| spellingShingle | Davide Bagnara Monica Colombo Daniele Reverberi Serena Matis Rosanna Massara Niccolò Cardente Gianluca Ubezio Vanessa Agostini Luca Agnelli Luca Agnelli Antonino Neri Martina Cardillo Stefano Vergani Fabio Ghiotto Fabio Ghiotto Andrea Nicola Mazzarello Fortunato Morabito Fortunato Morabito Giovanna Cutrona Manlio Ferrarini Franco Fais Franco Fais Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements Frontiers in Oncology chronic lymphocytic leukemia (CLL) immunoglobulin repertoire B-cells CD5 IGHV somatic mutations Ig light chain |
| title | Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements |
| title_full | Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements |
| title_fullStr | Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements |
| title_full_unstemmed | Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements |
| title_short | Characterizing Features of Human Circulating B Cells Carrying CLL-Like Stereotyped Immunoglobulin Rearrangements |
| title_sort | characterizing features of human circulating b cells carrying cll like stereotyped immunoglobulin rearrangements |
| topic | chronic lymphocytic leukemia (CLL) immunoglobulin repertoire B-cells CD5 IGHV somatic mutations Ig light chain |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.894419/full |
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