Pathological Significance of Anti-DNA Antibodies: analysis using monoclonal antibodies

系统性红斑狼疮(SLE)患者的特点是自发产生与DNA反应的抗体，这是该病中出现的肾炎和血管炎的原因之一。由于从SLE血清中提纯单特异性抗DNA抗体的难度较大，抗DNA抗体的准确特异性尚未明确。近年来，细胞杂交技术的进步部分解决了这一问题，这使得建立产生单特异性抗体的杂交瘤细胞系成为可能。利用这一技术，我们建立了几个抗SLE易感小鼠DNA的杂交瘤抗体克隆，B/W F1和MRL/LPR，并获得了证据表明，所有的单抗DNA抗体在其特异性方面表现出相当大的异质性。一个惊人的发现是，抗DNA单抗具有经常被观察到的多反应性，即与其他抗原结合的能力。这些反应包括1)DNA以外的核酸，2)磷脂，特别是心磷脂，3)Ciq和4)小鼠T和B细胞系以及有丝分裂原激活的脾细胞。

Patients with systemic lupus erythematosus (SLE) are charcterized by spontaneous production of antibodies reacting with DNA, which are one of the causative factors for developing nephritis and vasculitis seen in this disease. Because of difficulties in purifying monospecific anti-DNA antibodies from SLE sera, the prcise specificity of the anti-DNA antibodies has not yet been clearly defined. This problem recently can been settled in part by the advance in cell hybridization technique which makes feasible establish ment of hybrid cell lines producing monospecific antibodies.Using this technique, we established several clones of hybridoma antibodies to DNA from SLE-prone mouse, B/W F1 and MRL/lpr and obtained evidence that out monoclonal anti-DNA antibodies showed a considerable extent of heterogeneity in terms of their specificities. A striking finding was that the anti-DNA monoclonal antibodies have the frequently observed property of polyreactivity, i.e., the ability to bind to other antigens. These include reactivity to 1) nucleic acid other than DNA, 2) phospholipd, especially cardiolipn, 3) Ciq and 4) murine T and B cell lines and mitogen activated spleen cells.