Casali P, Burastero S E, Balow J E, Notkins A L
Laboratory of Oral Medicine, NIDR, Bethesda, MD 20892.
J Immunol. 1989 Dec 1;143(11):3476-83.
It was previously shown that human CD5+B cells are committed to the production of polyreactive "autoantibodies" that bind different self-Ag, including ssDNA, IgG Fc fragment, thyroglobulin, and insulin, as well as exogenous Ag, e.g., tetanus toxoid and other bacterial components. To define the contribution of the CD5+B cell subset to the production of antibodies to ssDNA in SLE, we quantitated, purified, and functionally characterized circulating CD5+ and CD5-B cells in patients and in healthy subjects. We found that in SLE patients circulating CD5+B cells were not increased in number, and both CD5+ and C5-B cells spontaneously secreted antibodies to ssDNA. Studies of the mAb we generated using CD5+ and CD5-B cells revealed that two types of antibody to ssDNA are produced in SLE. The first type, of the IgM class, is produced mainly by CD5+B cells and displays a moderate affinity for ssDNA (Kd, 10(-6) to 10(-7) mol/liter) and is polyreactive, not dissimilar to the autoantibodies inducible in the normal human B cell repertoire by polyclonal activation. The second type, mostly of the IgG and IgA class, is produced mainly by CD5-B cells and displays a higher affinity (Kd, 10(-8) mol/liter) for and reacts only with ssDNA. The functional features of the high affinity anti-ssDNA antibodies and the phenotype of their producing B cells mimic those characteristic of a "mature" Ag-driven response, such as that to tetanus toxoid in tetanus toxoid-vaccinated subjects.
先前的研究表明，人类CD5⁺B细胞致力于产生多反应性“自身抗体”，这些抗体可结合不同的自身抗原，包括单链DNA、IgG Fc片段、甲状腺球蛋白和胰岛素，以及外源性抗原，如破伤风类毒素和其他细菌成分。为了确定CD5⁺B细胞亚群对系统性红斑狼疮（SLE）中单链DNA抗体产生的贡献，我们对患者和健康受试者的循环CD5⁺和CD5⁻B细胞进行了定量、纯化和功能特性分析。我们发现，在SLE患者中，循环CD5⁺B细胞数量并未增加，并且CD5⁺和CD5⁻B细胞都会自发分泌单链DNA抗体。对我们使用CD5⁺和CD5⁻B细胞产生的单克隆抗体的研究表明，SLE中产生了两种类型的单链DNA抗体。第一种是IgM类，主要由CD5⁺B细胞产生，对单链DNA具有中等亲和力（解离常数Kd为10⁻⁶至10⁻⁷mol/升），具有多反应性，与正常人B细胞库中通过多克隆激活诱导产生的自身抗体并无不同。第二种主要是IgG和IgA类，主要由CD5⁻B细胞产生，对单链DNA具有更高的亲和力（Kd为10⁻⁸mol/升），并且仅与单链DNA反应。高亲和力抗单链DNA抗体及其产生B细胞的功能特征模仿了“成熟”抗原驱动反应的特征，例如破伤风类毒素接种受试者对破伤风类毒素的反应。
