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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31829d4d50
Epidemiology and Prevention

TLR2-Activated B Cells are Phenotypically Similar to the Abnormal Circulating B Cells Seen Preceding the Diagnosis of AIDS-Related NHL Diagnosis

Guo, Yu MD, PhD*,†,‡; Siewe, Basile PhD§; Epeldegui, Marta PhD*,‖; Detels, Roger MD*,¶; Landay, Alan L. PhD§; Martínez-Maza, Otoniel PhD*,‡,‖,¶,#

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Abstract

Background: AIDS-related non–Hodgkin lymphoma (AIDS-NHL) is a common AIDS-defining cancer. Prior studies suggest that chronic B-cell activation precedes AIDS-NHL diagnosis. Activation of B cells by multiple factors, including Toll-like receptor (TLR) signaling, leads to the expression of activation-induced cytidine deaminase (AID), a DNA mutating molecule that can contribute to oncogene translocations/mutations, leading to NHL. The goal of this study was to determine whether surface markers expressed on activated and/or germinal center B cells, and AID expression, were elevated on circulating B cells preceding AIDS-NHL and to determine if TLR signaling contributes to this activated B-cell phenotype.

Methods: Stored viable peripheral blood mononuclear cell specimens, obtained before AIDS-NHL diagnosis, were assessed by multicolor flow cytometry. Additionally, B cells isolated from peripheral blood mononuclear cell were exposed to TLR ligands in vitro, after which B-cell phenotype was assessed by flow cytometry.

Results: An elevated fraction of B cells expressing CD10, CD71, or CD86 was seen in those who went on to develop AIDS-NHL. AID expression was detected in some who developed AIDS-NHL, but not in HIV+ or HIV− controls. TLR2-stimulated purified B cells exhibited the activated B-cell phenotype observed in HIV+ subjects before AIDS-NHL diagnosis.

Conclusions: These results indicate that an elevated fraction of B cells display an activated/germinal center phenotype in those HIV+ subjects who go on to develop AIDS-NHL and suggest that TLR2-mediated activation may play a role in HIV infection–associated B-cell activation, potentially contributing to the genesis of AIDS-NHL.

© 2013 by Lippincott Williams & Wilkins

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