Kozono Y, Duke R C, Schleicher M S, Holers V M
Department of Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Eur J Immunol. 1995 Apr;25(4):1013-7. doi: 10.1002/eji.1830250423.
Recent studies have shown that complement receptors play important roles in both T-dependent and T-independent B lymphocyte responses to low doses of antigen (Ag) in vivo. Complement activation by either the classical or alternative pathway results in the covalent binding of C3 molecules to Ag in forms that ligate complement receptors type 1 (CR1) and 2 (CR2). We hypothesized that C3-bound Ag might cross-link CR2 and/or CR1 with surface (s)IgM and alter the signal that would be transduced through sIgM by Ag binding alone. One result of the altered signal could be the rescue of B lymphocytes from apoptosis that would otherwise be induced by the binding of certain types of Ag alone. We find that co-cross-linking of mouse CR2 and CR1 with sIgM rescues both resting B cells and WEHI-231.7 cells from apoptosis induced by sIgM ligation in a fashion similar to that found using soluble mouse CD40 ligand (mCD40L). Anti-CR2/CR1-mediated rescue requires co-cross-linking of the receptors with sIgM, and has an additive effect on mCD40L-mediated apoptosis rescue. Based on these results, it is likely that the CR2/CR1-derived signal is cooperative with T cell-derived signals such as CD40L and interleukin-4.
最近的研究表明，补体受体在体内低剂量抗原（Ag）刺激下的T细胞依赖性和非T细胞依赖性B淋巴细胞反应中均发挥重要作用。经典途径或替代途径激活补体，都会导致C3分子以连接补体受体1型（CR1）和2型（CR2）的形式共价结合到抗原上。我们推测，结合了C3的抗原可能会使CR2和/或CR1与表面（s）IgM发生交联，并改变仅通过抗原结合通过sIgM转导的信号。信号改变的一个结果可能是使B淋巴细胞免于凋亡，否则仅某些类型的抗原结合就会诱导凋亡。我们发现，小鼠CR2和CR1与sIgM的共交联可使静止B细胞和WEHI-231.7细胞免于由sIgM连接诱导的凋亡，其方式类似于使用可溶性小鼠CD40配体（mCD40L）所发现的方式。抗CR2/CR1介导的拯救需要受体与sIgM共交联，并且对mCD40L介导的凋亡拯救具有累加作用。基于这些结果，CR2/CR1衍生的信号很可能与T细胞衍生的信号如CD40L和白细胞介素-4协同作用。
