Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease
Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease
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DOI：
10.1016/j.jaci.2014.07.012
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发表时间：
2015-03-01
影响因子：
14.2
通讯作者：
Douagi, Iyadh
中科院分区：
文献类型：
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作者：
Cotugno, Nicola;Finocchi, Andrea;Douagi, Iyadh
背景：慢性肉芽肿病(CGD)是一种以活性氧产生缺陷为特征的原发免疫缺陷。虽然CGD的作用主要体现在吞噬间隔上，目的：探讨CGD和CGD携带者中gp91(Phox)表达缺陷对B细胞亚群和长期记忆维持的影响。方法：我们研究了CGD患者B细胞亚群的表型和产生活性氧物种的能力，以及针对B细胞受体和Toll样受体9不同刺激的增殖能力。我们通过测量细胞和血清学对测量的反应，进一步研究了他们维持长期记忆的能力。结果：我们发现CGD患者的记忆B细胞亚群受损，总(CD19(+)CD27(+))和静息(CD19(+)CD27(+)CD21(+))记忆性B细胞减少，而幼稚(CD19(+)CD27(-)IGD(+))B细胞频率增加。CGD携带者的数据显示，这种改变与gp91(Phox)的表达有关。此外，与年龄匹配的健康对照组相比，CGD患者B细胞体外选择性刺激B细胞受体或Toll样受体9通路的增殖能力降低。麻疹特异性抗体水平和抗体分泌细胞数量也显著降低，表明这些患者的长期记忆能力较差。结论：综上所述，我们的数据表明，CGD患者在记忆B细胞频率、对体外刺激的反应以及长期抗原特异性记忆的维持方面存在缺陷的B细胞室。
Background: Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD.Objective: We sought to investigate how defective gp91(phox) expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory.Methods: We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles.Results: We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD19(+)CD27(+)) and resting (CD19(+)CD27(+)CD21(+)) memory B cells in parallel to increased naive (CD19(+)CD27(-)IgD(+)) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91(phox) expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting cell numbers were also observed, indicating a poor ability to maintain long-term memory in these patients.Conclusion: Altogether, our data suggest that patients with CGD present a defective B-cell compartment in terms of frequencies of memory B cells, response to in vitro stimulation, and maintenance of long-term antigen-specific memory.