Abstract
HIV affects the function of all lymphocyte populations, including B cells. Phenotypic and functional defects of B cells in HIV-infected adults have been well characterized, but defects in children have not been studied to the same extent. We determined the proportion of B cell subsets and frequencies of Ag-specific memory B cells in peripheral blood from HIV-infected children and healthy controls, using flow cytometry and B cell ELISPOT, respectively. In addition, we measured the quantities and avidities of plasma Abs against various Ags by ELISA. We also determined plasma levels of BAFF and expression of BAFF receptors on B cells. Children with high HIV viremia had increased proportions of activated mature B cells, tissue-like memory B cells and plasmablasts, and low proportions of naive B cells when compared with community controls and children with low HIV viremia, similar to adults infected with HIV. HIV-infected groups had lower proportions of resting memory B cells than did community controls. Notably, high HIV viremia prevented the age-dependent accumulation of class-switched resting memory B cells. HIV-infected children, regardless of the level of viremia, showed lower quantities and avidities of IgG and lower frequencies of memory B cells against Expanded Program on Immunization vaccines. The HIV-infected children had an altered BAFF profile that could have affected their B cell compartment. Therefore, B cell defects in HIV-infected children are similar to those seen in HIV-infected adults. However, control of HIV viremia is associated with normalization of activated B cell subsets and allows age-dependent accumulation of resting memory B cells.
Highlights
Given that protection by Expanded Program on Immunization vaccines and immunity to common childhood pathogens often correlate with humoral responses, we investigated whether HIV-infected children developed memory B cells to the same extent as uninfected children or whether they showed the same defects in their B cell compartment as HIV-infected adults
In the first phase of the study, the distributions of B cell subsets were analyzed in 78 HIV-infected children, of whom 36 had high viremia and 42 had low viremia, and in 28 healthy community controls (Table I)
The proportions of activated mature B cells, tissue-like memory B cells, and plasmablasts were significantly increased in the high-viremia group, but not in the low-viremia group, when compared with community controls (Fig. 1)
Summary
In the first phase of the study, the distributions of B cell subsets were analyzed in 78 HIV-infected children, of whom 36 had high viremia and 42 had low viremia, and in 28 healthy community controls (Table I). Both the high- and low-viremia groups had lower proportions of total, switched, and unswitched resting memory B cells than did community controls.
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