TLR2-activated B cells are phenotypically similar to the abnormal circulating B cells seen preceding the diagnosis of AIDS-related NHL diagnosis

Yu Guo, Basile Siewe, Marta Epeldegui, Roger Detels, Alan L. Landay, Otoniel Martínez-Maza

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)204-210
Number of pages7
JournalJournal of Acquired Immune Deficiency Syndromes
Volume64
Issue number2
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

Keywords

  • Activation-induced cytidine deaminase
  • AIDS lymphoma
  • HIV
  • Non-Hodgkin lymphoma
  • Phenotype
  • Toll-like receptor

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

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