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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.

人系统性红斑狼疮产生自身抗体的机制：使用克隆 B 细胞后代和针对 B 细胞克隆的单克隆抗体分析机制。

基本信息

批准号：
61570312
负责人：
SAKANE Tsuyoshi
金额：
$ 1.54万
依托单位：
Shimane Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1987
项目状态：
已结题

项目摘要

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.

系统性红斑狼疮（SLE）患者体内存在的B细胞过度活跃可以通过几乎任何B细胞功能的测量来检测。然而，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物中的刺激反应迟钝。因此，SLE B细胞是否可能是内源性的高活性还有待确定。外周血SLE B细胞含有许多在体内已被激活的B细胞。然而，有必要分离“真正的”静息B细胞以在培养物中诱导B细胞过度活跃。为此，我们通过收集在Percoll密度梯度上以高密度级分沉淀的B细胞，获得了“真正的”静息B细胞。这些B细胞由小淋巴细胞组成，具有IgM和IgD，不表达活化抗原，并且不自发增殖。当暴露于金黄色葡萄球菌科万I（SAC）时，静止的SLE B细胞在体外以比正常B细胞高2至4倍的速率增殖。此外，SLE患者培养2天后获得显著增殖，而正常人培养开始3天后出现显著反应。此外，在Leu 1^+和Leu 1^- B细胞中，静止的SLE B细胞对SAC的增殖反应能力几乎相同。结果表明，SLE B细胞对触发刺激的多克隆方式的高兴奋性是疾病病因学中的主导因素。除了B细胞异常外，B细胞生长因子的过量产生也是SLE T细胞的共同特征。