Characterization of unique B-cell populations in the circulation of people living with HIV prior to non-Hodgkin lymphoma diagnosis

Laura E Martínez; Begoña Comin-Anduix; Miriam Güemes-Aragon; Javier Ibarrondo; Roger Detels; Matthew J Mimiaga; Marta Epeldegui

doi:10.3389/fimmu.2024.1441994

Characterization of unique B-cell populations in the circulation of people living with HIV prior to non-Hodgkin lymphoma diagnosis

Front Immunol. 2024 Sep 11:15:1441994. doi: 10.3389/fimmu.2024.1441994. eCollection 2024.

Authors

Laura E Martínez^{1

2}, Begoña Comin-Anduix^{3

4

5}, Miriam Güemes-Aragon^{3

6}, Javier Ibarrondo¹, Roger Detels⁷, Matthew J Mimiaga⁷, Marta Epeldegui^{1

2

3}

Affiliations

¹ UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, CA, United States.
² Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
³ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, United States.
⁴ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, United States.
⁵ Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Department of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
⁷ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, United States.

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.

Keywords: B regulatory cells; B-cells; HIV+ cART-naïve; HIV+ pre-NHL (cART-naïve); mass cytometry.

MeSH terms

Adult
B-Lymphocyte Subsets / immunology
B-Lymphocytes / immunology
Female
HIV Infections* / immunology
Humans
Immunophenotyping
Lymphoma, Non-Hodgkin / diagnosis
Lymphoma, Non-Hodgkin / immunology
Male
Middle Aged

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was funded in part by the National Institutes of Health (NIH)/National Cancer Institute (NCI) Grants R01-CA228157 and R21-CA220475; the UCLA Tumor Immunology T32 Training Grant and Postdoctoral Fellowship to LM (NCI Grant T32-CA009120); R01 Research Supplement to Promote Diversity in Health-Related Research to ME for LM from the NIH/NCI Grant R01-CA228157-S; a supplement from the UCLA Cancer Center Support Grant (NCI Grant P30-CA016042-S); and the UCLA AIDS Institute Center for AIDS Research (CFAR) (Division of Intramural Research, National Institute of Allergy and Infectious Diseases Grant P30-AI028697). In addition, this work was supported by the James B. Pendleton Charitable Trust and the McCarthy Family Foundation. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institute on Aging (NIA), National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Allergy And Infectious Diseases (NIAID), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Mental Health (NIMH), National Institute on Drug Abuse (NIDA), National Institute of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR).