CD27- B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection
CD27- B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection
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DOI：
10.1371/journal.pone.0005427
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发表时间：
2009-05-01
期刊：
影响因子：
3.7
通讯作者：
Nilsson, Anna
中科院分区：
文献类型：
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作者：
Cagigi, Alberto;Du, Likun;Nilsson, Anna
成熟的B细胞在抗原刺激下发生类转换重组和体细胞超突变。这些过程对于产生功能性抗体至关重要。在HIV-1感染期间，记忆B细胞的丧失，加上幼稚B细胞分化的改变，导致产生低质量的抗体，这可能是由于免疫球蛋白亲和力成熟受损所致。在本研究中，我们通过研究一组HIV-1慢性感染患者和一组健康对照组外周血B细胞中激活诱导型胞苷脱氨酶(AID)的表达，来评估HIV-1感染对类转换重组和体细胞超突变的影响。同时，我们还研究了B细胞的表型及其在体外产生免疫球蛋白的能力。来自HIV-1感染患者的细胞在体外以及CD40和TLR9刺激下显示出更高的基线水平的AID表达和增加的IgA产生。HIV-1感染者外周血中CD27(-)IgA(+)和CD27(-)Ig G(+)B细胞百分率明显高于对照组。有趣的是，我们的结果显示，患者CD27(-)细胞中VH基因的体细胞超突变数量显著增加。综上所述，这些结果表明，在HIV-1感染过程中，CD27(-)B细胞也可以产生类别转换和躯体高突变抗体。我们的数据为理解HIV-1感染期间观察到的特异性抗体产生丧失的机制提供了重要信息。
Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naive B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27(-) IgA(+) and CD27(-) IgG(+) B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27(-) cells from patients. Taken together, these results show that during HIV-1 infection, CD27(-) B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection.