Laura E. Martínez, Begoña Comin-Anduix, Miriam Güemes-Aragon, Javier Ibarrondo, Roger Detels, Matthew J. Mimiaga, Marta Epeldegui
{"title":"Characterization of unique B-cell populations in the circulation of people living with HIV prior to non-Hodgkin lymphoma diagnosis","authors":"Laura E. Martínez, Begoña Comin-Anduix, Miriam Güemes-Aragon, Javier Ibarrondo, Roger Detels, Matthew J. Mimiaga, Marta Epeldegui","doi":"10.3389/fimmu.2024.1441994","DOIUrl":null,"url":null,"abstract":"People living with HIV (PLWH) are at higher risk of developing lymphoma. In this study, we performed cytometry by time-of-flight (CyTOF) on peripheral blood mononuclear cells of cART-naïve HIV+ individuals and cART-naïve HIV+ individuals prior to AIDS-associated non-Hodgkin lymphoma (pre-NHL) diagnosis. Participants were enrolled in the Los Angeles site of the MACS/WIHS Combined Cohort Study (MWCCS). Uniform Manifold Approximation and Projection (UMAP) and unsupervised clustering analysis were performed to identify differences in the expression of B-cell activation markers and/or oncogenic markers associated with lymphomagenesis. CD10<jats:sup>+</jats:sup>CD27<jats:sup>-</jats:sup> B cells, CD20<jats:sup>+</jats:sup>CD27<jats:sup>-</jats:sup> B cells, and B-cell populations with aberrant features (CD20<jats:sup>+</jats:sup>CD27<jats:sup>+</jats:sup>CXCR4<jats:sup>+</jats:sup>CD71<jats:sup>+</jats:sup> B cells and CD20<jats:sup>+</jats:sup>CXCR4<jats:sup>+</jats:sup>cMYC<jats:sup>+</jats:sup> B cells) were significantly elevated in HIV+ cART-naïve compared to HIV-negative samples. CD20<jats:sup>+</jats:sup>CD27<jats:sup>+</jats:sup>CD24<jats:sup>+</jats:sup>CXCR4<jats:sup>+</jats:sup>CXCR5<jats:sup>+</jats:sup> B cells, CD20<jats:sup>+</jats:sup>CD27<jats:sup>+</jats:sup>CD10<jats:sup>+</jats:sup>CD24<jats:sup>+</jats:sup>CXCR4<jats:sup>+</jats:sup>cMYC<jats:sup>+</jats:sup> B cells, and a cluster of CD20<jats:sup>+</jats:sup>CXCR4<jats:sup>hi</jats:sup>CD27<jats:sup>-</jats:sup>CD24<jats:sup>+</jats:sup>CXCR5<jats:sup>+</jats:sup>CD40<jats:sup>+</jats:sup>CD4<jats:sup>+</jats:sup>AICDA<jats:sup>+</jats:sup> B cells were significantly elevated in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. A potentially clonal cluster of CD20<jats:sup>+</jats:sup>CXCR4<jats:sup>+</jats:sup>CXCR5<jats:sup>+</jats:sup>cMYC<jats:sup>+</jats:sup>AICDA<jats:sup>+</jats:sup> B cells and a cluster of germinal center B-cell-like cells (CD19<jats:sup>-</jats:sup>CD20<jats:sup>+</jats:sup>CXCR4<jats:sup>+</jats:sup>Bcl-6<jats:sup>+</jats:sup>PD-L1<jats:sup>+</jats:sup>cMYC<jats:sup>+</jats:sup>) were also found in the circulation of HIV+ pre-NHL (cART-naïve) samples. Moreover, significantly elevated clusters of CD19<jats:sup>+</jats:sup>CD24<jats:sup>hi</jats:sup>CD38<jats:sup>hi</jats:sup> cMYC<jats:sup>+</jats:sup> AICDA<jats:sup>+</jats:sup> B regulatory cells were identified in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. The present study identifies unique B-cell subsets in PLWH with potential pre-malignant features that may contribute to the development of pre-tumor B cells in PLWH and that may play a role in lymphomagenesis.","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"31 1","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2024.1441994","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
People living with HIV (PLWH) are at higher risk of developing lymphoma. In this study, we performed cytometry by time-of-flight (CyTOF) on peripheral blood mononuclear cells of cART-naïve HIV+ individuals and cART-naïve HIV+ individuals prior to AIDS-associated non-Hodgkin lymphoma (pre-NHL) diagnosis. Participants were enrolled in the Los Angeles site of the MACS/WIHS Combined Cohort Study (MWCCS). Uniform Manifold Approximation and Projection (UMAP) and unsupervised clustering analysis were performed to identify differences in the expression of B-cell activation markers and/or oncogenic markers associated with lymphomagenesis. CD10+CD27- B cells, CD20+CD27- B cells, and B-cell populations with aberrant features (CD20+CD27+CXCR4+CD71+ B cells and CD20+CXCR4+cMYC+ B cells) were significantly elevated in HIV+ cART-naïve compared to HIV-negative samples. CD20+CD27+CD24+CXCR4+CXCR5+ B cells, CD20+CD27+CD10+CD24+CXCR4+cMYC+ B cells, and a cluster of CD20+CXCR4hiCD27-CD24+CXCR5+CD40+CD4+AICDA+ B cells were significantly elevated in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. A potentially clonal cluster of CD20+CXCR4+CXCR5+cMYC+AICDA+ B cells and a cluster of germinal center B-cell-like cells (CD19-CD20+CXCR4+Bcl-6+PD-L1+cMYC+) were also found in the circulation of HIV+ pre-NHL (cART-naïve) samples. Moreover, significantly elevated clusters of CD19+CD24hiCD38hi cMYC+ AICDA+ B regulatory cells were identified in HIV+ pre-NHL (cART-naïve) compared to HIV+ cART-naïve samples. The present study identifies unique B-cell subsets in PLWH with potential pre-malignant features that may contribute to the development of pre-tumor B cells in PLWH and that may play a role in lymphomagenesis.
期刊介绍:
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.