TLR2-activated B cells are phenotypically similar to the abnormal circulating B cells seen preceding the diagnosis of AIDS-related NHL diagnosis.
J Acquir Immune Defic Syndr
; 64(2): 204-10, 2013 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-23722608
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfoma no Hodgkin
/
Linfocitos B
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Activación de Linfocitos
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Infecciones por VIH
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Linfoma Relacionado con SIDA
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Receptor Toll-Like 2
Tipo de estudio:
Clinical_trials
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Diagnostic_studies
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Observational_studies
/
Risk_factors_studies
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Año:
2013
Tipo del documento:
Article