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Memory B cell dysregulation in HIV-1 infected Individuals

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Abstract

Objective:

To characterize the effect of the HIV-1 infection and antiretroviral treatment (ART) in the human memory B (MEB) cell compartment.

Design:

A cross-sectional study was designed to analyze MEB cells of HIV-1+ ART-treated and ART-naïve subjects, and uninfected individuals.

Methods:

Frequency and absolute counts of MEB cell subsets in blood were determined by multicolor flow cytometry. Spontaneous cell death and B cell proliferative capacity was evaluated in vitro by cell culture and flow cytometry. Splenic function was determined by pitted erythrocytes quantification in HIV-1+ ART-treated subjects.

Results:

HIV-1+ ART-treated individuals did not show functional hyposplenism despite the lack of recovery IgM+IgD+CD27+ Marginal Zone-like B cells. Moreover, two Germinal Center (GC)-dependent MEB cells subsets were also dysregulated in HIV-1+ individuals: IgM+IgD-CD27+ (IgM-only) cells were increased whereas the switched subset (IgM-IgD-) was reduced in viremic individuals. Althought ART restored the numbers of these populations, the switched MEB cells were enriched in CD27- cells, which showed the highest susceptibility to spontaneous cell death ex vivo. In addition, B cells from viremic individuals showed a poor response to BCR and TLR9 stimulation that was circumvented when both stimuli were used simultaneously.

Conclusions:

B cells from HIV-1+ subjects show a poor stimulation capacity, that may be bypassed by the proper combination of stimuli, and a dysregulated MEB cell pool that suggest an affectation of the GC reaction, only partially normalized by ART. Interestingly, hyposplenism does not explain the lack of recovery of the Marginal Zone-like B cells in ART-treated HIV-1+ individuals.

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