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1. MZ lymphoproliferations: shared and unique characteristics

Author

Xochelli, Aliki, Bikos, Vasilis, Polychronidou, Eleftheria, Galigalidou, Chrysi, Agathangelidis, Andreas, Charlotte, Frédéric, Moschonas, Panagiotis, Davis, Zadie, Colombo, Monica, Roumelioti, Maria, Sutton, Lesley-Ann, Groenen, Patricia, van den Brand, Michiel, Boudjoghra, Myriam, Algara, Patricia, Traverse-Glehen, Alexandra, Ferrer, Ana, Stalika, Evangelia, Karypidou, Maria, Kanellis, George, Kalpadakis, Christina, Mollejo, Manuella, Pangalis, Gerasimos, Vlamos, Panayiotis, Amini, Rose-Marie, Pospisilova, Sarka, Gonzalez, David, Ponzoni, Maurilio, Anagnostopoulos, Achilles, Giudicelli, Véronique, Lefranc, Marie-Paule, Espinet, Blanca, Panagiotidis, Panagiotis, Piris, Miguel Angel, Du, Ming-Qing, Rosenquist, Richard, Papadaki, Theodora, Belessi, Chrysoula, Ferrarini, Manlio, Oscier, David, Tzovaras, Dimitrios, Ghia, Paolo, Davi, Frederic, Hadzidimitriou, Anastasia, Stamatopoulos, Kostas, Apollo - University of Cambridge Repository, Institute of Applied Biosciences, CERTH, Thessaloniki, Greece., Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden, Central European Institute of Technology [Brno] (CEITEC MU), Brno University of Technology [Brno] (BUT), Information Technologies Institute, CERTH, Thessaloniki, Greece., Department of Informatics, Ionian University, Corfu, Greece, Division of Experimental Oncology and Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy., Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Information Technologies Institute, CERTH, Thessaloniki, Greece, Department of Haematology, Royal Bournemouth Hospital, Bournemouth, UK., Molecular Pathology, Ospedale Policlinico SanMartino, Genoa, Italy., First Department of Propaedeutic Medicine, University of Athens, Athens, Greece, Uppsala Universitet [Uppsala], Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands., Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospital Virgen de la Salud, Toledo, Spain, Department of Pathology and Hematology, Hospices Civils de Lyon (HCL), Laboratori de Citologia Hematològica i Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain, Centre for Research and Technology Hellas (CERTH), Hematology Department and HCT Unit, G. Papanicolaou Hospital, Thessaloniki, Greece, Hematopathology Department, Evangelismos Hospital, Athens, Greece., Department of Haematology, University of Crete, Heraklion, Greece., Department of Haematology, Athens Medical Center, Athens, Greece, Department of Informatics [Ionian University], Ionian University [Corfu], Department of Informatics, Ionian University, Corfu, Greece., Department of Genetics and Pathology, Uppsala University Hospital, CEITEC-Central European Institute of Technology, MasarykBrno, Czech Republic., Pathology Unit, Unit of Lymphoid Malignancies, San Raffaele H Scientific Institute, Pathology Unit, San Raffaele Scientific Institute, Milan, Italy, Laboratoire d'ImmunoGénétique Moléculaire (LIGM), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoris de Citologia Hematológica/Citogenética Molecular. Servei de Patologia, GRETNHE, IMIM-Hospital del Mar, Laboratori de Citologia Hematològica i Citogenètica Molecular, Servei de Patologia, Hospital del Mar, Barcelona, Spain., Pathology Department, IIS 'Fundacion Jimenez Diaz', Madrid, Spain, Pathology, University of Cambridge [UK] (CAM), Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK, Hematology Department, Nikea General Hospital, Piraeus, Greece, Direzione Scientifica, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Azienda Ospedaliera Universitaria (AOU) San Martino-IST, Genoa, Italy., Informatics & Telematics Institute (ITI), CERTH, Università Vita e Salute, San Raffaele, Milano, Italy, Division of Experimental Oncology and Department of Onco-Hematology, IRCCS San Raffaele Scientific Institute and Università Vita-Salute San Raffaele, Milan, Italy, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Applied Biosciences, Centre for Research and Technology-Hellas, Thessaloniki, Greece, Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Sweden, Xochelli, Aliki, Bikos, Vasili, Polychronidou, Eleftheria, Galigalidou, Chrysi, Agathangelidis, Andrea, Charlotte, Frédéric, Moschonas, Panagioti, Davis, Zadie, Colombo, Monica, Roumelioti, Maria, Sutton, Lesley-Ann, Groenen, Patricia, van den Brand, Michiel, Boudjoghra, Myriam, Algara, Patricia, Traverse-Glehen, Alexandra, Ferrer, Ana, Stalika, Evangelia, Karypidou, Maria, Kanellis, George, Kalpadakis, Christina, Mollejo, Manuella, Pangalis, Gerasimo, Vlamos, Panayioti, Amini, Rose-Marie, Pospisilova, Sarka, Gonzalez, David, Ponzoni, Maurilio, Anagnostopoulos, Achille, Giudicelli, Véronique, Lefranc, Marie-Paule, Espinet, Blanca, Panagiotidis, Panagioti, Piris, Miguel Angel, Du, Ming-Qing, Rosenquist, Richard, Papadaki, Theodora, Belessi, Chrysoula, Ferrarini, Manlio, Oscier, David, Tzovaras, Dimitrio, Ghia, Paolo, Davi, Frederic, Hadzidimitriou, Anastasia, and Stamatopoulos, Kostas

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics, Genes, Immunoglobulin, Genes, Immunoglobulin Heavy Chain, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], [SDV]Life Sciences [q-bio], Immunoglobulin Variable Region, Receptors, Antigen, B-Cell, Lymphoma, B-Cell, Marginal Zone, Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9], Complementarity Determining Regions, marginal zone lymphoma, immunoglobulin gene, antigen, ontogeny, Marginal zone lymphoma, Mutation, Tumor Microenvironment, Humans, Gene Rearrangement, B-Lymphocyte
Abstract

Contains fulltext : 203155.pdf (Publisher’s version ) (Closed access) The B cell receptor immunoglobulin (Ig) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n = 488), i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL), as well as provisional entities (n = 76), according to the WHO classification. The most striking Ig gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different Ig gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ Ig sequence dataset with a large dataset of Ig sequences (MZ-related or not; n = 65 837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia, but also rheumatoid factors and non-malignant splenic MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments. Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Published
2019
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2. Depletion of T regulatory cells through selection of CD127-positive cells results in a population enriched in memory T cells: implications for anti-tumor cell therapy

Author

Soumia Touil, Charlotte Frédéric, Dan A. Landau, David Klatzmann, Philippe Le Corvoisier, José L. Cohen, Michelle Rosenzwajg, and Sébastien Maury

Subjects
Male, Lymphocyte, medicine.medical_treatment, Transplantation, Heterologous, Graft vs Host Disease, Mice, SCID, Hematopoietic stem cell transplantation, Biology, T-Lymphocytes, Regulatory, Lymphocyte Depletion, Donor lymphocyte infusion, Interleukin-7 Receptor alpha Subunit, Cell therapy, Mice, Immune system, Mice, Inbred NOD, medicine, Animals, Humans, Cytotoxic T cell, IL-2 receptor, Peripheral Blood Stem Cell Transplantation, FOXP3, Hematology, medicine.anatomical_structure, Immunology, Female, Original Articles and Brief Reports, Immunologic Memory
Abstract

Background Donor lymphocyte infusions can induce remissions in patients with relapse after allogeneic hematopoietic stem cell transplantation. Nevertheless, some grafted patients never display any signs of alloreactivity, either following allogeneic hematopoietic stem cell transplantation or after donor lymphocyte infusions. Consequently, they do not develop graft-versus-host disease and frequently do not respond to donor lymphocyte infusions. In a recently published clinical trial, we observed that elimination of CD4+CD25+Foxp3+ natural regulatory T cells from the donor lymphocyte product could improve alloreactivity and the associated anti-tumor effect in a small proportion of patients with relapsed hematologic malignancies. Here, we aimed to improve the effect of donor lymphocyte infusion by modifying the procedure for depletion of T regulatory cells.Design and Methods We directly compared depletion of regulatory T cells from human peripheral blood mononuclear cells achieved by selection of CD127-positive cells or by selection of CD25-negative cells. We tested the manipulated products (i) in vitro in mixed lymphocyte reactions and against pathogen-derived recall antigens and (ii) in vivo in experimental graft-versus-host disease.Results In vitro, we found that depletion of regulatory T cells through CD127 positive selection improved both alloreactive and pathogen-specific immune responses. In vivo, we observed accelerated donor T-cell division and enhanced graft-versus-host disease due to efficient regulatory T-cell depletion accompanied by enrichment in memory T cells.Conclusions Our results show that the strategy of CD127 positive selection is an efficient way of eliminating regulatory T cells from donor lymphocyte infusions and improves alloreactivity. This supports the investigation of CD127 positive selection in place of elimination of CD25-positive cells for clinical applications.

Published
2012
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3. Disease-biased and shared characteristics of the immunoglobulin gene repertoires in marginal zone B cell lymphoproliferations

Author

Xochelli, Aliki, Bikos, Vasilis, Polychronidou, Eleftheria, Galigalidou, Chrysi, Agathangelidis, Andreas, Charlotte, Frédéric, Moschonas, Panagiotis, Davis, Zadie, Colombo, Monica, Roumelioti, Maria, Sutton, Lesley-Ann, Groenen, Patricia, Van Den Brand, Michiel, Boudjoghra, Myriam, Algara, Patricia, Traverse-Glehen, Alexandra, Ferrer, Ana, Stalika, Evangelia, Karypidou, Maria, Kanellis, George, Kalpadakis, Christina, Mollejo, Manuella, Pangalis, Gerasimos, Vlamos, Panayiotis, Amini, Rose-Marie, Pospisilova, Sarka, Gonzalez, David, Ponzoni, Maurilio, Anagnostopoulos, Achilles, Giudicelli, Véronique, Lefranc, Marie-Paule, Espinet, Blanca, Panagiotidis, Panagiotis, Piris, Miguel Angel, Du, Ming-Qing, Rosenquist, Richard, Papadaki, Theodora, Belessi, Chrysoula, Ferrarini, Manlio, Oscier, David, Tzovaras, Dimitrios, Ghia, Paolo, Davi, Frederic, Hadzidimitriou, Anastasia, and Stamatopoulos, Kostas

Subjects
immunoglobulin gene, antigen, ontogeny, Marginal zone lymphoma, 3. Good health
Abstract

The B cell receptor immunoglobulin (BcR IG) gene repertoires of marginal zone (MZ) lymphoproliferations were analyzed in order to obtain insight into their ontogenetic relationships. Our cohort included cases with MZ lymphomas (n=488) i.e. splenic (SMZL), nodal (NMZL) and extranodal (ENMZL) as well as provisional entities (n=76) according to the World Health Organization classification. The most striking IG gene repertoire skewing was observed in SMZL. However, restrictions were also identified in all other MZ lymphomas studied, particularly ENMZL, with significantly different IG gene distributions depending on the primary site of involvement. Cross-entity comparisons of the MZ IG sequence dataset with a large dataset of IG sequences (MZ-related or not; n=65,837) revealed four major clusters of cases sharing homologous ('public') heavy variable complementarity-determining region 3. These clusters included rearrangements from SMZL, ENMZL (gastric, salivary gland, ocular adnexa), chronic lymphocytic leukemia but also rheumatoid factors and non-malignant spleen MZ cells. In conclusion, different MZ lymphomas display biased immunogenetic signatures indicating distinct antigen exposure histories. The existence of rare public stereotypes raises the intriguing possibility that common, pathogen-triggered, immune-mediated mechanisms, may result in diverse B lymphoproliferations due to targeting versatile progenitor B cells and/or operating in particular microenvironments.

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