Division of Microbiology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, Louisiana, United States of America.
PLoS One. 2011 Jan 27;6(1):e16524. doi: 10.1371/journal.pone.0016524.
Several B-cell defects arise in HIV infected patients, particularly in patients with chronic infection and high viral load. Loss of memory B cells (CD27(+) B cells) in peripheral blood and lymphoid tissues is one of the major B cell dysfunctions in HIV and simian immunodeficiency virus (SIV) infection. Despite several studies, definitive identification of memory B cells based on CD27 surface expression has not been described. Similarly, the rates of cell turnover in different B cell subpopulation from lymphoid and mucosal tissues have not been well documented. In this study, we demonstrate the presence of memory B cell populations and define their distribution, frequency and immunophenotype with regards to activation, proliferation, maturation, and antibody production in normal rhesus macaques from different lymphoid tissues.
METHODOLOGY/PRINCIPAL FINDINGS: Thirteen healthy, uninfected rhesus macaques were selected for this study. CD20(+) B cells were isolated from peripheral blood and sorted based on CD27 and CD21 surface markers to define memory B cell population. All the B cell subpopulation was further characterized phenotypically and their cell turnover rates were evaluated in vivo following bromodeoxyuridine (BrdU) inoculation. Double positive (DP) CD21(+)CD27(+) B cells in both peripheral and lymphoid tissues are memory B cells, able to produce antibody by polyclonal activation, and without T cell help. Peripheral and lymphoid DP CD21(+)CD27(+) B cells were also able to become activated and proliferate at higher rates than other B cell subpopulations. Increased turnover of tonsillar memory B cells were identified compared to other tissues examined.
CONCLUSIONS/SIGNIFICANCE: We suggest that this DP memory B cells play a major role in the immune system and their function and proliferation might have an important role in HIV/SIV mediated B cell dysregulation and pathogenesis.
在 HIV 感染患者中会出现几种 B 细胞缺陷,尤其是在慢性感染和高病毒载量的患者中。外周血和淋巴组织中记忆 B 细胞(CD27(+) B 细胞)的丧失是 HIV 和猴免疫缺陷病毒(SIV)感染中 B 细胞功能障碍的主要表现之一。尽管进行了多项研究,但仍未基于 CD27 表面表达对记忆 B 细胞进行明确鉴定。同样,尚未很好地记录来自淋巴和黏膜组织的不同 B 细胞亚群的细胞周转率。在这项研究中,我们证明了记忆 B 细胞群体的存在,并描述了它们的分布、频率和免疫表型,以及与正常食蟹猴不同淋巴组织中 B 细胞亚群的激活、增殖、成熟和抗体产生有关。
方法/主要发现:选择了 13 只健康、未感染的食蟹猴进行本研究。从外周血中分离出 CD20(+) B 细胞,根据 CD27 和 CD21 表面标志物进行分选,以定义记忆 B 细胞群体。所有 B 细胞亚群均进一步进行表型特征分析,并在体内用溴脱氧尿苷(BrdU)接种后评估其细胞周转率。外周和淋巴组织中的双阳性(DP)CD21(+)CD27(+) B 细胞均为记忆 B 细胞,能够通过多克隆激活产生抗体,无需 T 细胞辅助。外周和淋巴组织中的 DP CD21(+)CD27(+) B 细胞也能够以比其他 B 细胞亚群更高的速度激活和增殖。与检查的其他组织相比,发现扁桃体记忆 B 细胞的周转率增加。
结论/意义:我们认为,这种 DP 记忆 B 细胞在免疫系统中起着重要作用,其功能和增殖可能在 HIV/SIV 介导的 B 细胞失调和发病机制中具有重要作用。