B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy

Abstract

Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, peripheral blood B-cell counts were significantly lower in both early and chronic HIV-infected individuals compared with uninfected controls. Similar to CD4(+) but not CD8(+) T cells, B-cell numbers in both groups increased significantly after ART. At baseline, B cells of early HIV-infected individuals were composed of a higher percentage of plasmablasts and resting memory B cells compared with chronic HIV-infected individuals whose B cells were composed of a higher percentage of immature/transitional and exhausted B cells compared with their early infection counterparts. At 1 year after ART, the percentage of resting memory B cells remained higher in early compared with chronic HIV-infected individuals. This difference translated into a better functional profile in that memory B-cell responses to HIV and non-HIV antigens were superior in early- compared with chronic-treated HIV infected individuals. These findings provide new insights on B cells in HIV infection and how early initiation of ART may prevent irreversible immune system damage.

Figure 1

Lymphocyte counts in healthy individuals and early and chronically HIV-infected individuals before ART. Box plots of absolute lymphocyte numbers in the peripheral blood are shown for 3 groups of individuals: early and chronic HIV-infected individuals before initiation of therapy as well as HIV-uninfected individuals. Box plots include median with 25th and 75th percentile boarders and error bars represent 10th and 90th percentiles.

Figure 2

Changes in lymphocyte counts over time after initiation of ART. Absolute numbers of CD19⁺ B cells (A), CD4⁺ (B), and CD8⁺ (C) T cells in the peripheral blood were measured over time after initiation of ART at day 0. Each line represents the trajectory for 1 individual and was generated using regression from a minimum of 3 time points after initiation of ART. Left panels represent individuals treated early after infection and right panels represent individuals treated during the chronic stage of infection.

Figure 3

Distribution of B-cell subpopulations before and after ART in early and chronic HIV-infected individuals. The percentages of cells in each of the 6 B-cell subpopulations defined in the peripheral blood were measured for HIV-negative individuals and each group of HIV-infected individuals before (M0) and 12 months (M12) after ART.

Figure 4

Depiction of B cells before and after ART in early and chronic HIV-infected individuals. Expression of CD27 and CD21 on mature (CD10⁻) B cells isolated from the peripheral blood of 1 representative individual in each of the early- and chronic-treated groups before and 12 months after initiation of ART.

Figure 5

Memory B-cell responses to HIV and non-HIV antigens in early and chronic HIV-infected individuals. The frequencies of antibody-secreting cells (ASCs) against immobilized (A-B) and soluble (C-D) forms of monomeric HIV-1 gp120 envelope and against seasonal influenza (E-F) were measured by elispot after 4 days of culture. Responses were measured in 6 early (A,C,E) and 6 chronic (B,D,F) HIV-infected individuals before (M0) and 12 months after (M12) initiation of ART. While the majority of ASCs were of the IgG isotype, data represent total IgG, IgA, and IgM ASCs for each antigen. See supplemental Figure 1 for distribution of switched and unswitched isotypes and supplemental Figure 2 for total Ig ASC frequencies.