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.

点击翻译按钮获取中文摘要

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.