TY - JOUR
T1 - Memory B cell dysregulation in HIV-1-infected individuals
AU - Carrillo, Jorge
AU - Negredo, Eugènia
AU - Puig, Jordi
AU - Molinos-Albert, Luis Manuel
AU - Rodríguez De La Concepción, Maria Luisa
AU - Curriu, Marta
AU - Massanella, Marta
AU - Navarro, Jordi
AU - Crespo, Manel
AU - Viñets, Ester
AU - Millá, Fuensanta
AU - Clotet, Bonaventura
AU - Blanco, Julià
PY - 2018/1/14
Y1 - 2018/1/14
N2 - Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. 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-naive study participants, 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 study participants. 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-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 B-cell receptor and toll-like receptor 9 stimulation that was circumvented when both stimuli were used simultaneously. Conclusion: B cells from HIV-1 + study participants 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 germinal center 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. ©
AB - Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. 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-naive study participants, 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 study participants. 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-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 B-cell receptor and toll-like receptor 9 stimulation that was circumvented when both stimuli were used simultaneously. Conclusion: B cells from HIV-1 + study participants 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 germinal center 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. ©
KW - HIV-1
KW - antiretroviral treatment
KW - apoptosis
KW - immune system
KW - memory B cells
KW - splenic function
U2 - 10.1097/QAD.0000000000001686
DO - 10.1097/QAD.0000000000001686
M3 - Article
C2 - 29112067
SN - 0269-9370
VL - 32
SP - 149
EP - 160
JO - AIDS
JF - AIDS
IS - 2
ER -
