Control of Viremia Enables Acquisition of Resting Memory B Cells with Age and Normalization of Activated B Cell Phenotypes in HIV-Infected Children
Control of Viremia Enables Acquisition of Resting Memory B Cells with Age and Normalization of Activated B Cell Phenotypes in HIV-Infected Children
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DOI：
10.4049/jimmunol.1500491
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发表时间：
2015-08-01
影响因子：
4.4
通讯作者：
Urban, Britta C.
中科院分区：
文献类型：
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作者：
Muema, Daniel M.;Macharia, Gladys N.;Urban, Britta C.
HIV影响所有淋巴细胞群的功能，包括B细胞。HIV感染成人的B细胞的表型和功能缺陷已得到很好的表征，但儿童的缺陷尚未得到同样程度的研究。我们分别用流式细胞术和B细胞ELISPOT法测定了HIV感染儿童和健康儿童外周血中B细胞亚群的比例和Ag特异性记忆B细胞的频率。此外，我们通过ELISA测量了针对各种Ag的血浆Ab的数量和亲和力。我们还测定了BAFF的血浆水平和B细胞上BAFF受体的表达。与社区对照组和低HIV病毒血症儿童相比，高HIV病毒血症儿童的活化成熟B细胞、组织样记忆B细胞和浆母细胞比例增加，幼稚B细胞比例较低，与感染HIV的成人相似。HIV感染组的静息记忆B细胞比例低于社区对照组。值得注意的是，高HIV病毒血症阻止了类别转换的静息记忆B细胞的年龄依赖性积累。HIV感染的儿童，无论病毒血症的水平，显示出较低的数量和亲和力的IgG和较低的频率的记忆B细胞对扩大免疫计划疫苗。HIV感染儿童的BAFF谱发生改变，可能影响了他们的B细胞区室。因此，HIV感染儿童的B细胞缺陷与HIV感染成人相似。然而，HIV病毒血症的控制与活化的B细胞亚群的正常化相关，并允许静息记忆B细胞的年龄依赖性积累。
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.