Suzuki N, Sakane T, Engleman E G
Department of Pathology, Stanford University, California 94305.
J Clin Invest. 1990 Jan;85(1):238-47. doi: 10.1172/JCI114418.
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.
尽管抗DNA抗体的存在是系统性红斑狼疮（SLE）的一个标志，但分泌抗DNA抗体的B细胞亚群以及负责诱导抗DNA分泌的刺激因素均尚不明确。特别是，CD5⁺ B细胞在人类SLE中的作用尚不清楚，而在SLE小鼠模型中，CD5⁺ B细胞是一个独特的抗体分泌细胞亚群，先前已被证明是抗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）检测方法，用于测量15例SLE患者和15名健康对照者的纯化CD5⁺和CD5⁻ B细胞对单链（ss）DNA、双链（ds）DNA、破伤风类毒素和多克隆免疫球蛋白（Ig）的自发抗体分泌。15名健康受试者中只有1人的B细胞分泌了显著水平的抗ssDNA抗体，且无人分泌抗dsDNA抗体。相比之下，在大多数SLE患者中，CD5⁺和CD5⁻ B细胞均分泌IgG和/或IgM抗ssDNA以及抗dsDNA抗体。对抗ssDNA反应的进一步分析显示，CD5⁻ B细胞分泌的IgG和IgM抗DNA抗体水平与同一亚群的多克隆Ig产生水平密切相关（分别为r = 0.81和0.70）。相比之下，CD5⁺ B细胞产生抗DNA的过程独立于CD5⁺和CD5⁻ B细胞亚群的多克隆Ig产生。这些结果表明，在人类SLE中存在两个产生抗DNA抗体的B细胞亚群，其诱导机制不同：一个（CD5⁺）独立分泌抗DNA，另一个（CD5⁻）作为多克隆B细胞激活的明显结果产生抗DNA。
