title: TLR2-activated B cells are phenotypically similar to the abnormal circulating B cells seen preceding the diagnosis of AIDS-related NHL diagnosis.
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.
authors.affiliation: *UCLA AIDS Institute, Los Angeles, CA; †The Institution of Viral disease Control and Prevention, CDC, Beijing, China; ‡Departments of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, CA; §Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL; ‖Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA; ¶Department of Epidemiology, UCLA Jonathan and Karin Fielding School of Public Health, Los Angeles, CA; and #Jonsson Comprehensive Cancer Center, Los Angeles, CA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Guo
authors.forename: Basile
authors.initials: B
authors.lastname: Siewe
authors.forename: Marta
authors.initials: M
authors.lastname: Epeldegui
authors.forename: Roger
authors.initials: R
authors.lastname: Detels
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D016483:Lymphoma, AIDS-Related / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase