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Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection.

Abstract：

OBJECTIVES:Microbial translocation and chronic immune activation were previously shown to be associated with impairment of T cell functions and disease progression during infection with human immunodeficiency virus type-1 (HIV-1); however, their impact on B cell function and number remains unknown. By measuring markers of immune activation and molecules involved in apoptosis regulation, we have evaluated the association between microbial translocation and loss of memory B cells in HIV-1-infected patients. METHODS:Markers of activation [the interleukin-21 receptor (IL-21R) and CD38] and apoptosis (Bim, Bcl-2 and annexin V) were measured in B cell subpopulations by multicolour flow cytometry. Levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS), measures of microbial translocation, were determined in plasma. Purified B cells were also exposed in vitro to Toll-like receptor (TLR) ligands. RESULTS:IL-21R expression was higher in cells from HIV-1-infected patients, compared with control subjects, with the highest levels in nontreated patients. An inverse correlation was observed between IL-21R expression and percentages of circulating resting memory (RM) B cells. IL-21R-positive memory B cells were also more susceptible to spontaneous apoptosis and displayed lower levels of Bcl-2. It is interesting that the levels of sCD14, which are increased during HIV-1 infection, were correlated with decreased percentages of RM B cells and high IL-21R expression. In the plasma of HIV-1-infected individuals, a correlation was found between sCD14 and LPS levels. TLR activation of B cells in vitro resulted in IL-21R up-regulation. CONCLUSIONS:Microbial translocation and the associated immune activation during HIV-1 infection may lead to high expression levels of the IL-21R activation marker in RM B cells, a feature associated with increased apoptosis and a reduced number of these cells in the circulation.

journal_name

J Intern Med

journal_title

Journal of internal medicine

authors

Ruffin N,Lantto R,Pensieroso S,Sammicheli S,Hejdeman B,Rethi B,Chiodi F

doi

10.1111/j.1365-2796.2012.02550.x

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

492-503

issue

eissn

0954-6820

issn

1365-2796

journal_volume

272

pub_type

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Immune activation and increased IL-21R expression are associated with the loss of memory B cells during HIV-1 infection.