Haba S, Thorbecke G J, Nisonoff A
Department of Biology, Rosenstiel Research Center, Brandeis University, Waltham, MA 02254.
Proc Natl Acad Sci U S A. 1988 Apr;85(7):2293-7. doi: 10.1073/pnas.85.7.2293.
High titers of autoantibodies directed to isotypic determinants of IgD were produced by inoculation of syngeneic monoclonal IgD, conjugated covalently to keyhole limpet hemocyanin, into adult or neonatal inbred mice. Anti-idiotypic antibodies were induced at the same time. The average affinity of the mouse antibodies (Ka approximately equal to 10(7) M-1) is similar to that of rabbit anti-IgD and of syngeneic anti-IgE induced by the same procedure. Results indicate that B cells of the mice are not tolerant to serum IgD and that tolerance is maintained at the level of T cells. Direct interaction of the syngeneic anti-IgD with cell-surface IgD was minimal, and there was no convincing evidence that cell-surface IgD was down-regulated in the anti-IgD-producing mice. Further studies, preferably employing monoclonal anti-IgD, are required to determine whether epitopes on cell-surface IgD can be recognized by syngeneic anti-IgD. The ability to generate in vivo high titers of anti-IgD should facilitate the production of such monoclonal antibodies.
通过将与钥孔血蓝蛋白共价结合的同基因单克隆IgD接种到成年或新生近交小鼠体内,可产生针对IgD同种型决定簇的高滴度自身抗体。同时诱导出抗独特型抗体。小鼠抗体的平均亲和力(Ka约等于10(7) M-1)与通过相同程序诱导的兔抗IgD和同基因抗IgE相似。结果表明,小鼠的B细胞对血清IgD不耐受,且耐受性维持在T细胞水平。同基因抗IgD与细胞表面IgD的直接相互作用极小,且没有令人信服的证据表明在产生抗IgD的小鼠中细胞表面IgD被下调。需要进一步研究,最好使用单克隆抗IgD,以确定细胞表面IgD上的表位是否能被同基因抗IgD识别。在体内产生高滴度抗IgD的能力应有助于此类单克隆抗体的产生。