Mechanism of autoantibody production in human systemic lupus erythematosus: analysis of the mechanism using clonal B cell progenies and monoclonal antibodies to the B cell clones.

系统性红斑狼疮(SLE)患者体内存在的B细胞过度活动几乎可以通过任何B细胞功能的测量来检测到。尽管如此，B细胞过度活跃的基础很难在体外研究。相反，SLE B细胞更有可能对培养中的刺激反应迟钝。因此，系统性红斑狼疮B细胞是否存在内源性高活性仍有待确定。外周血中含有大量体内活化的B细胞。然而，有必要分离“真正的”静息B细胞，以在培养中诱导B细胞过度活动。为此，我们通过收集在Percoll密度梯度上以高密度部分沉淀的B细胞来获得“真正的”静止B细胞。这些B细胞由小淋巴细胞组成，同时具有IgM和IGD，不表达激活抗原，不能自发增殖。静止期SLE B细胞在金黄色葡萄球菌Cowan I(SAC)作用下的体外增殖率是正常B细胞的2~4倍。此外，SLE患者在培养2天后获得显著的增殖，而正常人在开始培养3天后出现明显的反应。此外，静息状态下的SLE B细胞对SAC的反应能力在Leu1^+和Leu1^-B细胞中几乎相同。结果表明，SLE B细胞对触发刺激的多克隆方式的兴奋性增强是该病病因的主导因素。除了B细胞的异常外，B细胞生长因子的过度产生也是SLE T细胞的共同特征。

B cell hyperactivity present in the body in patients with systemic lupus erythematosus (SLE) can be detectable via almost any measure of B cell function. Nonetheless, the basis for the B cell hyperactivity is difficult to study in vitro. Rather, the SLE B cells are more likely to hyporespond to stimuli in culture. Therefore, it remains to be determined whether SLE B cells may be endogenously hyperactive.Peripheral blood SLE B cells contain many B cells that have been activated in vivo. However, it is necessary to isolate "genuine" resting B cells to induce B cell hyperactivity in culture. To this end, we have obtained the "genuine" resting B cells by collecting B cells sedimenting in a high density fraction on a Percoll density gradient. These B cells consist of small lymphocytes, have both IgM and IgD, do not express activation antigens, and do not proliferate spontaneously.The resting SLE B cells proliferated in vitro at a 2 to 4 fold higher rate then normal B cells when exposed to Staphylococcus aureus Cowan I (SAC). In addition, significant proliferation was obtained after 2 days of culture in SLE patients, whereas significant response appeared 3 days after initiation of culture in normals. Moreover, the ability of the resting SLE B cells to proliferate in response to SAC was virtually identical among Leu 1^+ and Leu 1^- B cells. The results argue for a hightened excitability in a polyclonal manner of the SLE B cells to triggering stimuli as a dominant factor in the etiology of the disease. In addition to the abnormalities with B cells, excessive production of B cell growth factors is also a common feature of SLE T cells.