Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection
Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection
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DOI：
10.1182/blood-2003-07-2375
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发表时间：
2004-03-15
期刊：
影响因子：
20.3
通讯作者：
Chiodi, F
中科院分区：
文献类型：
--
作者：
De Milito, A;Nilsson, A;Chiodi, F
高丙种球蛋白血症和体液免疫缺陷是HIV-1感染的标志。幼稚B细胞最近被认为是慢性病毒感染中高丙种球蛋白血症的主要来源。我们最近报道HIV-1感染者携带低水平的记忆B细胞。我们研究了HIV-1感染患者幼稚和记忆B细胞的缺陷是否会转化为高丙种球蛋白血症和针对特定抗原的体液免疫缺陷。来自HIV-1感染患者的幼稚B细胞表现出活化/分化标志物CD 70和白细胞相关Ig样受体（LAIR-1）的异常表达。来自患者的活化初始B细胞显示出离体细胞内免疫球蛋白G（IgG）含量的显著增加，并且这种活化表型与高丙种球蛋白血症和来自患者的初始B细胞在体外分泌IgG的能力相关。我们分析了与记忆B细胞相关的破伤风类毒素、麻疹和HIV-1抗体水平，并观察到低记忆B淋巴细胞患者的抗原特异性抗体显著降低。然而，高丙种球蛋白血症和多特异性自身反应抗体水平在正常和低记忆B细胞患者中是相当的。我们的结论是，减少记忆B淋巴细胞在HIV-1感染与体液免疫缺陷和过度活化的幼稚B细胞可能代表的来源异常IgG产生的HIV-1感染。我们的研究结果可能与HIV-1治疗性疫苗的设计和HIV-1感染患者的临床管理有关。(C)2004年，美国血液学会。
Hypergammaglobulinemia and defective humoral immunity are hallmarks of HIV-1 infection. Naive B cells have been recently suggested as the major source of hypergammaglobulinemia in chronic viral infections. We recently reported that HIV-1-infected patients carry low levels of memory B cells. Here we studied whether defects in the naive and memory B cells in HIV-1-infected patients translated into hypergammaglobulinemia and defective humoral immunity against specific antigens. Naive B cells from HIV-1-infected patients exhibited abnormal expression of the activation/differentiation markers CD70 and leukocyte-associated Ig-like receptor (LAIR-1). Activated naive B cells from patients showed a significant increase in the intracellular immunoglobulin G (IgG) content ex vivo and this activated phenotype correlated to hypergammaglobulinemia and to the ability of naive B cells from patients to secrete IgG in vitro. We analyzed the levels of antibodies to tetanus toxoid, measles, and HIV-1 in relation to memory B cells and observed a significant reduction of antigen-specific antibodies in patients with low-memory B lymphocytes. Nevertheless, hypergammaglobulinemla and levels of polyspecific self-reactive antibodies were comparable in patients with normal and low memory B cells. We conclude that reduction of memory B lymphocytes in HIV-1 infection correlates with defective humoral immunity and that hyperactivated naive B cells may represent the source of abnormal IgG production in HIV-1 infection. Our results may be relevant to the design of HIV-1 therapeutical vaccines and to the clinical management of HIV-1-infected patients. (C) 2004 by The American Society of Hematology.