Vaccine Branch, National Cancer Institute, Bethesda, Maryland, USA.
J Virol. 2012 Dec;86(23):12591-604. doi: 10.1128/JVI.00298-12. Epub 2012 Sep 12.
Human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection causes B-cell dysregulation and the loss of memory B cells in peripheral blood mononuclear cells (PBMC). These effects are not completely reversed by antiretroviral treatment (ART). To further elucidate B-cell changes during chronic SIV infection and treatment, we investigated memory B-cell subpopulations and plasma cells/plasmablasts (PC/PB) in blood, bone marrow, and lymph nodes of rhesus macaques during ART and upon release from ART. Macaques previously immunized with SIV recombinants and the gp120 protein were included to assess the effects of prior vaccination. ART was administered for 11 weeks, with or without gp120 boosting at week 9. Naïve and resting, activated, and tissue-like memory B cells and PC/PB were evaluated by flow cytometry. Antibody-secreting cells (ASC) and serum antibody titers were assessed. No lasting changes in B-cell memory subpopulations occurred in bone marrow and lymph nodes, but significant decreases in numbers of activated memory B cells and increases in numbers of tissue-like memory B cells persisted in PBMC. Macaque PC/PB were found to be either CD27(+) or CD27(-) and therefore were defined as CD19(+) CD38(hi) CD138(+). The numbers of these PC/PB were transiently increased in both PBMC and bone marrow following gp120 boosting of the unvaccinated and vaccinated macaque groups. Similarly, ASC numbers in PBMC and bone marrow of the two macaque groups also transiently increased following envelope boosting. Nevertheless, serum binding titers against SIVgp120 remained unchanged. Thus, even during chronic SIV infection, B cells respond to antigen, but long-term memory does not develop, perhaps due to germinal center destruction. Earlier and/or prolonged treatment to allow the generation of virus-specific long-term memory B cells should benefit ART/therapeutic vaccination regimens.
人类免疫缺陷病毒（HIV）/猴免疫缺陷病毒（SIV）感染导致外周血单个核细胞（PBMC）中的 B 细胞失调和记忆 B 细胞丧失。这些影响不能通过抗逆转录病毒治疗（ART）完全逆转。为了进一步阐明慢性 SIV 感染和治疗期间 B 细胞的变化，我们研究了接受 ART 治疗和停止 ART 后恒河猴血液、骨髓和淋巴结中的记忆 B 细胞亚群和浆细胞/浆母细胞（PC/PB）。包括之前用 SIV 重组体和 gp120 蛋白免疫的恒河猴，以评估先前疫苗接种的影响。ART 治疗持续 11 周，第 9 周时加用或不加用 gp120 加强。通过流式细胞术评估幼稚和静止、激活和组织样记忆 B 细胞和 PC/PB。评估抗体分泌细胞（ASC）和血清抗体滴度。骨髓和淋巴结中 B 细胞记忆亚群没有持久变化，但 PBMC 中激活的记忆 B 细胞数量减少，组织样记忆 B 细胞数量增加。发现恒河猴 PC/PB 要么是 CD27(+)，要么是 CD27(-)，因此被定义为 CD19(+) CD38(hi) CD138(+)。未接种疫苗和接种疫苗的恒河猴组在 gp120 加强后，PBMC 和骨髓中的 PC/PB 数量均短暂增加。同样，两组恒河猴 PBMC 和骨髓中的 ASC 数量在包膜加强后也短暂增加。然而，针对 SIVgp120 的血清结合滴度保持不变。因此，即使在慢性 SIV 感染期间，B 细胞也会对抗原产生反应，但不会产生长期记忆，这可能是由于生发中心破坏。更早和/或更长时间的治疗以允许产生病毒特异性长期记忆 B 细胞，将有益于 ART/治疗性疫苗接种方案。
