Elevated numbers of PD-L1 expressing B cells are associated with the development of AIDS-NHL

• Published in: Scientific reports Vol. 9; no. 1; p. 9371
• Main Authors: Epeldegui, Marta, Conti, David V., Guo, Yu, Cozen, Wendy, Penichet, Manuel L., Martínez-Maza, Otoniel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.06.2019; Nature Publishing Group
• Subjects: 13; 13/1; 13/106; 13/21; 13/31; 631/250; 631/250/249/1570/1901; Acquired immune deficiency syndrome; AIDS; Apoptosis; CD19 antigen; CD38 antigen; CD40 antigen; CD40L protein; Cell activation; Cell death; Diagnosis; Epstein-Barr virus; Etiology; Flow cytometry; HIV; Human immunodeficiency virus; Humanities and Social Sciences; Immunoregulation; Interleukin 1; Interleukin 10; Lymphocytes B; Lymphocytes T; Lymphoma; multidisciplinary; Non-Hodgkin's lymphoma; PD-1 protein; PD-L1 protein; Peripheral blood mononuclear cells; Science; Science (multidisciplinary); Virions
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-45479-3

The risk for non-Hodgkin lymphoma (NHL) is markedly increased in persons living with human immunodeficiency virus (HIV) infection, and remains elevated in those on anti-retroviral therapy (cART). Both the loss of immunoregulation of Epstein-Barr virus (EBV) infected cells, as well as chronic B-cell activation, are believed to contribute to the genesis of AIDS-related NHL (AIDS-NHL). However, the mechanisms that lead to AIDS-NHL have not been completely defined. A subset of B cells that is characterized by the secretion of IL10, as well as the expression of the programmed cell death ligand-1 (PD-L1/CD274), was recently described. These PD-L1 + B cells can exert regulatory function, including the dampening of T-cell activation, by interacting with the program cell death protein (PD1) on target cells. The role of PD-L1 + B cells in the development of AIDS-NHL has not been explored. We assessed B cell PD-L1 expression on B cells preceding AIDS-NHL diagnosis in a nested case-control study of HIV+ subjects who went on to develop AIDS-NHL, as well as HIV+ subjects who did not, using multi-color flow cytometry. Archival frozen viable PBMC were obtained from the UCLA Multicenter AIDS Cohort Study (MACS). It was seen that the number of CD19 + CD24 ++ CD38 ++ and CD19 + PD-L1 + cells was significantly elevated in cases 1–4 years prior to AIDS-NHL diagnosis, compared to controls, raising the possibility that these cells may play a role in the etiology of AIDS-NHL. Interestingly, most PD-L1 + expression on CD19 + cells was seen on CD19 + CD24 ++ CD38 ++ cells. In addition, we showed that HIV can directly induce PD-L1 expression on B cells through interaction of virion-associated CD40L with CD40 on B cells.