Memory B Cell Function in HIV-Infected Children—Decreased Memory B Cells Despite ART

Abstract

B cell dysfunction is a well-studied complication of HIV infection in adults. Data on B cell differentiation in normal and HIV-infected children are lacking. We show the distribution of B cell subsets and immunoglobulin levels in HIV-infected children compared with controls. Furthermore, we observe the long-term B cell reconstitution of vaccine-specific immunity after antiretroviral therapy (ART). Phenotype of B cells (naive, non-switched memory, switched memory) was analyzed in 48 infected children and 62 controls. In nine HIV-infected children, functional reconstitution was quantified by tetanus-specific antibodies and by performing a lymphocyte transformation test (LTT) in a longitudinal approach.

B‐cell responses to HIV infection

“…Normalization of B-cell populations and functionalities has been shown to occur when HIV viremia is suppressed by therapy (63, 98, 144–151), especially when treatment is initiated early during the course of infection (24, 152). Resting memory B cells, the cells responsible for long-lasting memory in healthy individuals (44), are particularly vulnerable to the deleterious effects of persistent HIV replication and immune activation, with many reports demonstrating only partial restoration following reduction of viremia by ART (24, 144, 149–151). A few studies have reported that a “normal” distribution of the circulating B-cell populations in certain HIV-infected individuals, similar to that observed in healthy uninfected individuals, is associated with broad HIV-specific memory B-cell responses or bNAbs (153, 154).…”

HIV-associated memory B cell perturbations

“…Some studies report that circulating un-switched memory B cells, defined by surface expression of CD19+CD27+IgD+, are preferentially depleted in HIV-infected children and adults [25, 29], while the other studies claim that class switched memory B cells (CD20+CD27+IgD−) were depleted more profoundly in pediatric HIV infection [30], suggesting that immature immunity plays a role in B cell class switching. When IgM− is used to represent switched memory B cells, CD19+CD27+IgM−switched memory B cells are depleted in HIV infected individuals irrespective of antiretroviral status [31].…”

Immune reconstitution and vaccination outcome in HIV-1 infected children

“…59 However, we have shown that antibodies to tetanus toxoid remain high (to levels comparable to age-matched healthy individuals) for several years after DTP in children treated with HAART before 1 y of age compared with children also having Many studies on DTP (mostly analyzing immunity to tetanus toxoid) involving re-vaccination of children on HAART are available. 52,[54][55][56][57][58][59][60][61] The percentage of initial responders to vaccination ranged 53-100% among different studies 52,56,[58][59][60][61] while in general, a high percentage of children (up to 90%) maintained immunity to tetanus for 1 y after vaccination. 52,59,61 Only one study reported a significant decline in the percentage of responders (from 74% to 38%) before 1 y from vaccination.…”

“…56 For pertussis, the antibody concentration was analyzed in one study showing a decline over-time (from 22.3 EU/mL at 2 mo to 6.8 EU/mL at 2 y from vaccination). 57 Lymphoproliferative responses within 3 mo from vaccination were also evaluated for tetanus toxoid in several studies showing a proportion of 47-86% of responders 52,54,55,59 while one study reported that only 17% of Standard, alternative and possible predictive markers for evaluating clinical protection upon immunization of Hiv-1 infected children. Th1-2, CD4 + T helper 1 or 2 cells; Tc, CD8 + Cytotoxic T-cells; eiA, enzyme immunoassay; eLiSA, enzyme-linked immunosorbent assay; eLiSpot, enzyme-linked immunosorbent spot; FAMA, fluorescent antibody membrane assay; gpeLiSA, glycoprotein eLiSA; HAi, haemagglutination inhibition assay, LPA, lymphoproliferation assay; OPA, opsonophagocytic activity assay; SBA, serum bactericidal antibody assay; Si, stimulation index.…”