Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.
Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus.
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DOI：
10.1172/jci114418
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发表时间：
1990
期刊：
影响因子：
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通讯作者：
Noboru Suzuki;Tsuyoshi Sakane;E. G. Engleman
中科院分区：
文献类型：
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作者：
Noboru Suzuki;Tsuyoshi Sakane;E. G. Engleman
尽管抗DNA抗体的存在是系统性红斑狼疮（SLE）的标志，但分泌抗DNA抗体的B细胞亚群和负责诱导抗DNA分泌的刺激物都是未知的。特别是，CD 5 + B细胞在人SLE中的作用是未知的，CD 5 + B细胞是一种独特的抗体分泌细胞亚群，以前被证明是SLE小鼠模型中抗DNA抗体的来源。为了解决这些问题，我们开发了一种灵敏的酶联免疫斑点（ELIspot）检测15例SLE患者和15例健康对照者的纯化CD 5+和CD 5- B细胞自发分泌的单链（ss）DNA，双链（ds）DNA，破伤风类毒素和多克隆免疫球蛋白（IG）抗体。15名健康受试者中只有1名的B细胞分泌显著水平的抗ssDNA抗体，没有人分泌抗dsDNA。相反，在大多数SLE患者中，CD 5+和CD 5- B细胞都分泌IgG和/或IgM抗ssDNA以及抗dsDNA抗体。抗ssDNA应答的进一步分析显示，CD 5- B细胞分泌IgG和IgM抗DNA抗体的水平与同一亚群产生多克隆IG的水平密切相关（r分别为0.81和0.70）。相反，CD 5 + B细胞产生抗DNA与CD 5+和CD 5- B细胞亚群产生多克隆IG无关。这些结果表明，在人类SLE中存在两种具有不同诱导机制的产生抗DNA抗体的B细胞亚群：一种（CD 5+），其独立地分泌抗DNA，另一种（CD 5-），其产生抗DNA作为多克隆B细胞活化的明显结果。
Although the presence of anti-DNA antibody is a hallmark of systemic lupus erythematosus (SLE), neither the subsets of B cells that secrete anti-DNA antibody nor the stimuli responsible for the induction of anti-DNA secretion is known. In particular, the role of CD5+ B cells in human SLE, a distinct subpopulation of antibody-secreting cells shown previously to be a source of anti-DNA antibody in murine models of SLE, is unknown. To approach these questions, we developed a sensitive enzyme-linked immunospot (ELIspot) assay to measure spontaneous secretion of antibody to single-stranded (ss) DNA, double-stranded (ds) DNA, tetanus toxoid, and polyclonal immunoglobulin (Ig) by purified CD5+ and CD5- B cells of 15 SLE patients and 15 healthy control subjects. The B cells of only 1 of 15 healthy subjects secreted a significant level of anti-ssDNA antibody, and none secreted anti-dsDNA. By contrast, in the majority of SLE patients both CD5+ and CD5- B cells secreted IgG and/or IgM anti-ssDNA as well as anti-dsDNA antibody. Further analysis of the anti-ssDNA response revealed that the level of IgG and IgM anti-DNA antibody secretion by CD5- B cells correlated closely with the level of polyclonal Ig production by the same subpopulation (r = 0.81 and 0.70, respectively). In contrast, production of anti-DNA by CD5+ B cells occurred independently of polyclonal Ig production by both CD5+ and CD5- B cell subpopulations. These results suggest that in human SLE there exist two anti-DNA antibody-producing B cell subpopulations with distinct induction mechanisms: one (CD5+), which independently secretes anti-DNA, and another (CD5-), which produces anti-DNA as an apparent consequence of polyclonal B cell activation.