Cragg M S, Zhang L, French R R, Glennie M J
Tenovus Research Laboratory, Southampton General Hospital, UK.
Br J Cancer. 1999 Feb;79(5-6):850-7. doi: 10.1038/sj.bjc.6690136.
In vitro studies identified three Burkitts lymphoma cell lines, Ramos, MUTU-I and Daudi, that were growth inhibited by anti-IgM antibody. However, only Ramos and MUTU-I were sensitive to monoclonal antibodies (mAb) recognizing the Fc region of surface IgM (anti-Fc mu). Experiments using anti-Fc mu mAb (single or non-crossblocking pairs), polyclonal anti-mu Ab, and hyper-crosslinking with a secondary layer of Ab, showed that growth inhibition of B-cell lines was highly dependent on the extent of IgM crosslinking. This was confirmed by using Fab', F(ab')2 and F(ab')3 derivatives from anti-Fc mu mAb, where increasing valency caused corresponding increases in growth arrest and apoptosis, presumably as a result of more efficient BCR-crosslinking on the cell surface. The ability of a single mAb to induce growth arrest was highly dependent on epitope specificity, with mAb specific for the Fc region (C mu2-C mu4 domains) being much more effective than those recognizing the Fab region (anti-L chain, anti-Id and anti-Fd mu, or C mu1). Only when hyper-crosslinked with polyclonal anti-mouse IgG did the latter result in appreciable growth inhibition. Binding studies showed that these differences in function were not related to differences in the affinity, but probably related to intrinsic crosslinking capacity of mAb.
体外研究鉴定出三种伯基特淋巴瘤细胞系，即拉莫斯细胞系、MUTU-I细胞系和多迪细胞系，它们会受到抗IgM抗体的生长抑制。然而，只有拉莫斯细胞系和MUTU-I细胞系对识别表面IgM的Fc区域的单克隆抗体（抗Fcμ）敏感。使用抗Fcμ单克隆抗体（单克隆或非交叉阻断对）、多克隆抗μ抗体以及用第二层抗体进行超交联的实验表明，B细胞系的生长抑制高度依赖于IgM交联的程度。这通过使用抗Fcμ单克隆抗体的Fab'、F(ab')2和F(ab')3衍生物得到证实，其中价数增加导致生长停滞和凋亡相应增加，这可能是由于细胞表面BCR交联更有效所致。单个单克隆抗体诱导生长停滞的能力高度依赖于表位特异性，对Fc区域（Cμ2 - Cμ4结构域）具有特异性的单克隆抗体比识别Fab区域（抗轻链、抗独特型和抗Fdμ或Cμ1）的单克隆抗体更有效。只有在用多克隆抗小鼠IgG进行超交联时，后者才会导致明显的生长抑制。结合研究表明，这些功能差异与亲和力差异无关，而可能与单克隆抗体的内在交联能力有关。
