Barrett T B, Shu G, Clark E A
Department of Microbiology, University of Washington, Seattle 98195.
J Immunol. 1991 Mar 15;146(6):1722-9.
Cell-cell adhesion events play critical roles in the sequential migrations and multiple specific cell-cell interactions which B cells undergo during normal development and function. We have observed that mAb to several B cell-associated molecules, including mAb to CD19, CD37, and CD40, induce homotypic aggregation of freshly isolated human B cells. The aggregation of B cells induced by CD40 mAb was due to activation of a cell-cell adhesion system, and not due to agglutination by mAb, because 1) in addition to being energy dependent and cation dependent, the aggregation was blocked by inhibitors of messenger RNA and protein synthesis; and 2) a mouse B cell line transformed with intact human CD40 aggregated in response to CD40 mAb, whereas a line expressing surface CD40, but lacking the cytoplasmic tail and previously shown incapable of transmitting a signal from the cell surface, did not aggregate. The aggregation, although of slow onset, was persistent and of high avidity. In addition, CD40 mAb induced increased surface expression of intercellular adhesion molecule-1 (CD54), a ligand for CD11a/CD18 (LFA-1), and CD18 mAb blocked aggregation. CD40 mAb also augmented the ability of dense B cells to stimulate the proliferation of allogeneic T cells via a CD18-dependent process. We conclude that signaling through CD40, elicited by cross-linking the CD40 protein on the cell surface, activates the CD18/intercellular adhesion molecule adhesion system; in addition, CD40 cross-linking may activate a second adhesion system since CD40 mAb induced aggregation of the B cell line Ramos, which does not express surface CD18. B cell adhesion may be triggered by signaling through multiple surface proteins, thereby lending specificity of activation to adhesion systems which are broadly expressed.
细胞间黏附事件在B细胞正常发育和功能过程中经历的一系列迁移和多种特定细胞间相互作用中发挥着关键作用。我们观察到，针对几种B细胞相关分子的单克隆抗体，包括针对CD19、CD37和CD40的单克隆抗体，可诱导新鲜分离的人B细胞发生同型聚集。CD40单克隆抗体诱导的B细胞聚集是由于细胞间黏附系统的激活，而非单克隆抗体的凝集作用，原因如下：1）除了能量依赖性和阳离子依赖性外，聚集还被信使RNA和蛋白质合成抑制剂所阻断；2）用完整的人CD40转化的小鼠B细胞系对CD40单克隆抗体有聚集反应，而表达表面CD40但缺乏细胞质尾巴且先前已证明无法从细胞表面传递信号的细胞系则无聚集反应。这种聚集虽然起始缓慢，但持续存在且亲和力高。此外，CD40单克隆抗体可诱导细胞间黏附分子-1（CD54，CD11a/CD18（LFA-1）的配体）的表面表达增加，而CD18单克隆抗体可阻断聚集。CD40单克隆抗体还通过依赖CD18的过程增强了密集B细胞刺激同种异体T细胞增殖的能力。我们得出结论，通过交联细胞表面的CD40蛋白引发的CD40信号传导可激活CD18/细胞间黏附分子黏附系统；此外，CD40交联可能激活第二个黏附系统，因为CD40单克隆抗体可诱导不表达表面CD18的B细胞系Ramos发生聚集。B细胞黏附可能由通过多种表面蛋白的信号传导触发，从而赋予广泛表达的黏附系统激活特异性。
