Mongini P K, Vilensky M A, Highet P F, Inman J K
Department of Rheumatology and Molecular Medicine, Hospital for Joint Diseases, New York, New York, 10003, USA.
Cell Immunol. 1998 Sep 15;188(2):137-50. doi: 10.1006/cimm.1998.1359.
Culture of human B lymphocytes with polyclonally activating surrogates for type II T-cell-independent antigen, i.e., anti-IgM mAb and anti-IgM:dextran, resulted in both membrane IgM (mIgM)-triggered S/G2/M entry and apoptosis. Although high ligand valency could compensate for low affinity, and high affinity could compensate for low valency, in achieving mIgM-triggered apoptosis, the phenomenon was most pronounced when the soluble "antigen" had both high binding site affinity and valency. Most of the mIgM-triggered apoptosis may represent B cells which progress into G1 but fail to receive a sufficient level of continuous mIgM-mediated signaling during G1 for passage through a G1 --> S phase restriction point(s). This was supported by the findings that (a) a lesser proportion of mIg-triggered cells enter S phase than G1; (b) maximal mIgM-triggered apoptosis was noted at 48-72 h of culture and surrounding activated cell clusters; (c) mIgM-triggered apoptosis was not inhibited by pharmacologic blockers of S phase; and (d) a high proportion of viable mIgM-triggered B cell blasts in G1 succumb to apoptosis rather than enter S phase, if high-affinity multivalent ligand is washed from the cultures. In addition to quantitative aspects of initial receptor engagement, the potential for a protracted period of recurrent mIgM signaling events may influence whether apoptosis or cell cycle progression is the functional outcome of B cell encounter with a multivalent antigen.
用多克隆激活替代物培养人B淋巴细胞，这些替代物用于II型非T细胞依赖性抗原，即抗IgM单克隆抗体和抗IgM：葡聚糖，导致膜IgM（mIgM）触发的S/G2/M期进入和细胞凋亡。尽管高配体价可以补偿低亲和力，高亲和力可以补偿低价，但在实现mIgM触发的细胞凋亡方面，当可溶性“抗原”同时具有高结合位点亲和力和价时，这种现象最为明显。大多数mIgM触发的细胞凋亡可能代表进入G1期但在G1期未能获得足够水平的持续mIgM介导信号以通过G1→S期限制点的B细胞。以下发现支持了这一点：（a）与进入G1期相比，mIg触发进入S期的细胞比例较低；（b）在培养48 - 72小时时，在周围活化细胞簇中观察到最大的mIgM触发的细胞凋亡；（c）mIgM触发的细胞凋亡不受S期药物阻滞剂的抑制；（d）如果从培养物中洗去高亲和力多价配体，G1期大量存活的mIgM触发的B细胞母细胞会发生凋亡而不是进入S期。除了初始受体结合的定量方面外，长时间反复发生的mIgM信号事件的可能性可能会影响细胞凋亡或细胞周期进展是否是B细胞与多价抗原相遇的功能结果。
