Finkelman F D, Villacreses N, Holmes J M
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
J Immunol. 1992 Dec 15;149(12):3845-50.
The injection of mice with a goat or rabbit antibody to mouse IgD stimulates a large polyclonal IgG response, approximately 10% of which is specific for antigenic determinants on the anti-IgD antibody molecule. The large goat IgG (GIgG)-specific antibody response in mice injected with goat antibody to mouse IgD requires that GIgG-specific B cells undergo much greater clonal expansion than B cells specific for other Ag. One possible explanation for the greater clonal expansion of GIgG-specific B cells is that B cells that lack GIgG specificity can only be stimulated with GIgG-specific T help during the relatively short time that anti-IgD binds to, and is processed and presented by, these B cells before they cease to express membrane mIgD. In contrast, GIgG-specific B cells can continue to bind, process, and present GIgG through mIgM after they lose mIgD. To test the hypothesis that extended stimulation with Ag-specific T help is required to generate a specific antibody response, we determined time requirements for Ag-specific T cell help for the development of such a response. Mice were injected with rabbit antibody to mouse IgD plus one or more daily injections of FITC conjugated to a F(ab')2 fragment of rabbit IgG (FITC-(Fab')2), which has a short in vivo half-life, and IgG1 anti-FITC antibody production was analyzed. In this system, each additional injection of FITC-F(ab')2 extends the period during which FITC-specific B cells can process this Ag and present it to rabbit IgG-specific T cells. Each additional injection of FITC-F(ab')2 stimulated a several-fold increase in IgG1 anti-FITC antibody levels, and injections on 5 consecutive days were required to induce a maximal anti-FITC response. These observations provide evidence that sustained Ag-specific T cell help is required to stimulate the degree of B cell clonal expansion that characterizes a specific antibody response.
给小鼠注射抗小鼠IgD的山羊或兔抗体可刺激产生大量多克隆IgG反应，其中约10%针对抗IgD抗体分子上的抗原决定簇具有特异性。给小鼠注射抗小鼠IgD的山羊抗体后，小鼠体内产生的针对山羊IgG（GIgG）的特异性抗体反应很强，这要求GIgG特异性B细胞比其他抗原特异性B细胞经历更大程度的克隆扩增。GIgG特异性B细胞克隆扩增程度更高的一种可能解释是，缺乏GIgG特异性的B细胞只有在抗IgD与这些B细胞结合、被处理并呈递的相对较短时间内，才能受到GIgG特异性T细胞辅助的刺激，之后这些B细胞就会停止表达膜IgD。相比之下，GIgG特异性B细胞在失去mIgD后，可通过mIgM继续结合、处理并呈递GIgG。为了验证产生特异性抗体反应需要抗原特异性T细胞辅助进行延长刺激这一假说，我们确定了抗原特异性T细胞辅助产生这种反应所需的时间要求。给小鼠注射抗小鼠IgD的兔抗体，再加上每天注射一次或多次与兔IgG的F(ab')2片段偶联的异硫氰酸荧光素（FITC-(Fab')2），其在体内半衰期较短，然后分析IgG1抗FITC抗体的产生情况。在这个系统中，每次额外注射FITC-F(ab')2都会延长FITC特异性B细胞处理该抗原并将其呈递给兔IgG特异性T细胞的时间。每次额外注射FITC-F(ab')2都会刺激IgG1抗FITC抗体水平增加几倍，并且需要连续5天注射才能诱导出最大的抗FITC反应。这些观察结果证明，需要持续的抗原特异性T细胞辅助来刺激B细胞克隆扩增程度，这是特异性抗体反应的特征。
