Parry S L, Hasbold J, Holman M, Klaus G G
Laboratory of Cellular Immunology, National Institute for Medical Research, Mill Hill, London, UK.
J Immunol. 1994 Mar 15;152(6):2821-9.
Cross-linking of sIgM or sIgD receptors on mature B cells with appropriate anti-Ig Abs normally induces B cell activation and DNA synthesis. We show here that hypercross-linking of either class of sIg receptor on these cells by biotinylated, normally mitogenic anti-mu or anti-delta mAb by avidin rapidly induces unresponsiveness to heterologous anti-Ig, accompanied by DNA fragmentation characteristic of apoptosis. Apoptotic nuclei can be detected within 4 h after stimulation, but cells that survive for 12 to 16 h are abortively activated, as evidenced by increased levels of MHC class II Ags. Because the induction of B cell tolerance is known to be modulated by T cell-derived influences, we investigated the effects of two stimuli--IL-4 and ligation of CD40--that are known to affect B cell survival in this system. IL-4 partially reversed the induction of apoptosis, as did a mAb to CD40, and both reagents together caused almost complete reversal. We therefore conclude that in the absence of T cell help the extent of sIg receptor cross-linking on mature B cells determines whether the cells enter cycle or become deleted. We believe that this system represents a polyclonal model of clonal deletion of mature B cells induced by highly cross-linking Ags, such as type 2 T-independent polysaccharide Ags.
用适当的抗Ig抗体使成熟B细胞上的sIgM或sIgD受体交联通常会诱导B细胞活化和DNA合成。我们在此表明，通过抗生物素蛋白使生物素化的、通常具有促有丝分裂作用的抗μ或抗δ单克隆抗体对这些细胞上的任何一类sIg受体进行过度交联，会迅速诱导细胞对异源抗Ig无反应，并伴有凋亡特有的DNA片段化。刺激后4小时内即可检测到凋亡细胞核，但存活12至16小时的细胞会被异常激活，这可通过MHC II类抗原水平的升高得到证明。由于已知B细胞耐受性的诱导受T细胞衍生影响的调节，我们研究了两种已知会影响该系统中B细胞存活的刺激因素——IL-4和CD40的连接——的作用。IL-4部分逆转了凋亡的诱导，抗CD40单克隆抗体也有此作用，两种试剂共同作用几乎完全逆转。因此，我们得出结论，在没有T细胞帮助的情况下，成熟B细胞上sIg受体交联的程度决定了细胞是进入周期还是被清除。我们认为，该系统代表了由高度交联抗原（如2型非T细胞依赖性多糖抗原）诱导的成熟B细胞克隆清除的多克隆模型。
