Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

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.

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

Epeldegui

Conti

Guo

et al. 2019

Sci Rep

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Clinical significance and prognostic value of circulating B10 cells in colorectal cancer

Qiu

et al. 2021

Asia-Pac J Clncl Oncology

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Background: B10 cells, a subset of regulatory B cells, can inhibit antitumor response and thus promote tumor development. This study explored the clinical meaning and prognostic value of circulating B10 cells in colorectal cancer (CRC). Materials and methods:The proportion of B10 cells in peripheral blood in CRC patients and healthy controls was detected by multicolor flow cytometry. Results:The proportion of circulating B10 cells was remarkably elevated in CRC patients compared to normal controls (% of CD19 + B cells; 16.6% (IQR 6.0%) versus 9.0% (IQR 5.7%), p < 0.001). B10 cells proportion was associated with tumor size, depth of invasion, lymph node metastasis, and TNM stage in CRC. Kaplan-Meier analysis indicated that CRC patients with high B10 cells proportion suffered worse overall survival than those with low B10 cells proportion. Multivariate analysis revealed that the proportion of B10 cells was an independent prognostic indicator for CRC patients. Conclusion:Our results indicate that the proportion of circulating B10 cells is an independent prognostic factor for patients with CRC and thus may help guide the clinical decision in CRC.

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Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Cited by 2 publications

References 34 publications

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

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

Clinical significance and prognostic value of circulating B10 cells in colorectal cancer

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