AUTHOR=Martínez Laura E. , Comin-Anduix Begoña , Güemes-Aragon Miriam , Ibarrondo Javier , Detels Roger , Mimiaga Matthew J. , Epeldegui Marta TITLE=Characterization of unique B-cell populations in the circulation of people living with HIV prior to non-Hodgkin lymphoma diagnosis JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1441994 DOI=10.3389/fimmu.2024.1441994 ISSN=1664-3224 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⁺CXCR4^hiCD27^-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⁺CD24^hiCD38^hi 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.