Kozono Y, Abe R, Kozono H, Kelly R G, Azuma T, Holers V M
Research Institute for Biological Science, Science University of Tokyo, Chiba, Japan.
J Immunol. 1998 Feb 15;160(4):1565-72.
Activation of the complement cascade and ligation of complement C3 receptors on B cells represent an important bridge between innate and Ag-specific acquired immunity. We show here that cross-linking of mouse CD21 (complement receptor type 2, CR2, C3d receptor) and CD35 (complement receptor type 1, CR1, C3b/C4b receptor) or co-cross-linking of CD21/CD35 and surface IgM rapidly up-regulates both B7-1 and B7-2 expression on murine resting splenic B cells. CD21/CD35-mediated up-regulation of both B7-1 and B7-2 expression is observed within 14 h, while other stimuli up-regulate only B7-2 but not B7-1 at this early time point. Consistent with the increase in B7 levels, BALB/c B cells on which surface IgM and CD21/CD35 have been co-cross-linked stimulate C57BL/6 T cells more effectively than controls. This CD21/CD35-enhanced allogeneic MLR is blocked nearly completely by anti-B7-2 mAbs and partially by anti-B7-1 mAbs. In addition, cross-linking of CD19, which is physically associated with CD21/CD35, leads to increased B7-1 and B7-2 expression. These data suggest that CD21/CD35 ligation results in enhanced B cell Ag presentation using costimulatory mechanisms shared with other activators and thus works cooperatively in this process. Rapid up-regulation of B7-1 expression, a unique response to CD21/CD35 and CD19 cross-linking, may be a particularly important effect of C3-containing ligands. We propose that CD21/CD35- and CD19-mediated B7-1 and B7-2 up-regulation is an important mechanism by which complement activation links innate and acquired immunity.
补体级联反应的激活以及B细胞上补体C3受体的连接代表了天然免疫和抗原特异性获得性免疫之间的重要桥梁。我们在此表明，小鼠CD21（补体受体2型，CR2，C3d受体）和CD35（补体受体1型，CR1，C3b/C4b受体）的交联或CD21/CD35与表面IgM的共交联可迅速上调小鼠静息脾B细胞上B7-1和B7-2的表达。在14小时内观察到CD21/CD35介导的B7-1和B7-2表达上调，而在这个早期时间点，其他刺激仅上调B7-2而不上调B7-1。与B7水平的增加一致，表面IgM和CD21/CD35已被共交联的BALB/c B细胞比对照更有效地刺激C57BL/6 T细胞。这种CD21/CD35增强的同种异体混合淋巴细胞反应几乎完全被抗B7-2单克隆抗体阻断，部分被抗B7-1单克隆抗体阻断。此外，与CD21/CD35物理相关的CD19的交联导致B7-1和B7-2表达增加。这些数据表明，CD21/CD35连接通过与其他激活剂共享的共刺激机制导致B细胞抗原呈递增强，因此在这个过程中协同发挥作用。B7-1表达的快速上调是对CD21/CD35和CD19交联的独特反应，可能是含C3配体的特别重要的作用。我们提出，CD21/CD35和CD19介导的B7-1和B7-2上调是补体激活连接天然免疫和获得性免疫的重要机制。
