Murakami M, Kumagai S, Sugita M, Iwai K, Imura H
Second Division of Internal Medicine, School of Medicine, Kyoto University, Japan.
Clin Exp Immunol. 1992 Nov;90(2):245-50. doi: 10.1111/j.1365-2249.1992.tb07936.x.
An HLA-DR restricted T cell clone (26G11) which recognized a lymphoid cell-derived autoantigen associated with DR4 molecule was shown to induce not only autologous but also allogenic DR4+ B cells to produce large amounts of antibodies of the IgG and IgM classes. Using the helper activity of this clone, we investigated the mechanism of anti-DNA antibody production in DR-matched patients with systemic lupus erythematosus (SLE). When cultured with 26G11 cells, B cells from DR-matched normal control subjects produced large amounts of IgM anti-DNA antibody, but did not produce IgG anti-DNA antibody which is thought to have a pathological role in SLE. In contrast, B cells from DR-matched patients with active SLE spontaneously produced a fairly large amount of IgG anti-DNA antibody, and the production was augmented by the T cell clone. Little IgG anti-DNA antibody was produced by the B cells of patients with inactive SLE in either the presence or absence of T cell clone. We next fractionated B cells into low density B (LD-B) and high density B (HD-B) cells by centrifugation on discontinuous Percoll density gradients. IgG anti-DNA antibody was spontaneously produced by LD-B cells of active SLE patients but not by those either of inactive SLE patients or normal controls. On the other hand, although IgG anti-DNA antibody was not spontaneously produced by the HD-B cells of both active and inactive SLE patients, it could easily be induced by their culture with the T cell clone. Our results clearly show the existence of IgG anti-DNA antibody-producing B cells in the peripheral blood of SLE patients irrespective of their disease activity and suggest that autoreactive T cells may play a pathogenic role in SLE through the induction of autoantibody production.
一个HLA - DR限制性T细胞克隆（26G11），它识别一种与DR4分子相关的淋巴样细胞衍生自身抗原，已被证明不仅能诱导自身DR4 + B细胞，还能诱导同种异体DR4 + B细胞产生大量IgG和IgM类抗体。利用该克隆的辅助活性，我们研究了DR匹配的系统性红斑狼疮（SLE）患者中抗DNA抗体产生的机制。当与26G11细胞共培养时，DR匹配的正常对照受试者的B细胞产生大量IgM抗DNA抗体，但不产生被认为在SLE中具有病理作用的IgG抗DNA抗体。相比之下，DR匹配的活动性SLE患者的B细胞自发产生相当大量的IgG抗DNA抗体，并且T细胞克隆增强了这种产生。无论是在有还是没有T细胞克隆的情况下，非活动性SLE患者的B细胞产生的IgG抗DNA抗体都很少。接下来，我们通过在不连续的Percoll密度梯度上离心将B细胞分为低密度B（LD - B）细胞和高密度B（HD - B）细胞。活动性SLE患者的LD - B细胞自发产生IgG抗DNA抗体，而非活动性SLE患者或正常对照的LD - B细胞则不产生。另一方面，虽然活动性和非活动性SLE患者的HD - B细胞都不自发产生IgG抗DNA抗体，但通过与T细胞克隆共培养很容易诱导产生。我们的结果清楚地表明，无论疾病活动状态如何，SLE患者外周血中都存在产生IgG抗DNA抗体的B细胞，并提示自身反应性T细胞可能通过诱导自身抗体产生在SLE中发挥致病作用。
