Malynn B A, Romeo D T, Wortis H H
J Immunol. 1985 Aug;135(2):980-8.
Previous experiments suggested a role for specific B cells in the induction of antigen (SRBC)-specific T cell proliferation. Two models were proposed: in the first, B cells directly presented antigen to T cells; alternatively, B cells secreted antibody, which opsonized antigen for presentation by macrophages. Experiments to distinguish between these possibilities are presented here. Three lines of evidence support the conclusion that antigen is presented directly by specific B cells. First, nonimmune splenic adherent cells (SAC), which efficiently induced proliferation of appropriately primed T cells to antigens such as OVA and GAT, were unable to induce SRBC-specific proliferation. Secondly, a slope analysis of the logarithmic plot of T cell proliferation vs the number of irradiated B cells suggested that two cells were limiting within the presenting population. The addition of IL 1 or SAC reduced the slope to 1 (although in serum-free conditions, the addition of IL 1, but not SAC, reduced the slope of the line). Specificity of the B cells for the antigen continued to be required in the presence of exogenous IL 1 or SAC. These results suggested that presentation by specific B cells and the amount of IL 1 were the limiting requirements for the induction of SRBC-specific T cell proliferation. The third line of evidence was the demonstration of a restricted interaction between T cells and B cells. The addition of irradiated, allogeneic SRBC-specific B cells to T cell lines and syngeneic SAC failed to support proliferative responses. We further show that a GAT-specific T cell clone was triggered to proliferate by either SAC or B cells, but that antigen-specific B cells were necessary at low doses of antigen. This finding is important in two respects. First, the T cell clone previously has been shown to act as a helper; secondly, when low doses of antigen are used, the requirement for priming of the B cells to the specific antigen is true for a soluble, as well as a particulate, antigen. We propose that at low (physiologic) doses of antigen, presentation to secondary T cells takes place mainly at the surface of antigen-specific B cells. At high doses of antigen,h presentation can also be accomplished by nonspecific cells such as other B cells, macrophages, or dendritic cells.
先前的实验表明特定B细胞在诱导抗原(绵羊红细胞,SRBC)特异性T细胞增殖中发挥作用。提出了两种模型:第一种,B细胞直接向T细胞呈递抗原;另一种,B细胞分泌抗体,抗体调理抗原以便巨噬细胞呈递。本文展示了区分这些可能性的实验。三条证据支持抗原由特定B细胞直接呈递这一结论。第一,非免疫脾黏附细胞(SAC)能有效诱导经适当致敏的T细胞对诸如卵清蛋白(OVA)和谷氨酸-丙氨酸-酪氨酸聚合物(GAT)等抗原发生增殖,但无法诱导SRBC特异性增殖。第二,对T细胞增殖对数图与经辐照的B细胞数量进行斜率分析表明,呈递细胞群体中两个细胞起限制作用。添加白细胞介素1(IL-1)或SAC可将斜率降至1(尽管在无血清条件下,添加IL-1而非SAC可降低直线斜率)。在外源IL-1或SAC存在的情况下,仍需要B细胞对抗原具有特异性。这些结果表明特定B细胞的呈递以及IL-1的量是诱导SRBC特异性T细胞增殖的限制因素。第三条证据是证明了T细胞与B细胞之间存在受限的相互作用。将经辐照的同种异体SRBC特异性B细胞添加到T细胞系和同基因SAC中无法支持增殖反应。我们进一步表明,一个GAT特异性T细胞克隆可被SAC或B细胞触发增殖,但在低剂量抗原时,抗原特异性B细胞是必需的。这一发现有两个重要方面。第一,先前已证明该T细胞克隆起辅助作用;第二,当使用低剂量抗原时,对于可溶性抗原以及颗粒性抗原,B细胞对特定抗原进行致敏的要求都是成立的。我们提出,在低(生理)剂量抗原时,向二级T细胞的呈递主要发生在抗原特异性B细胞表面。在高剂量抗原时,呈递也可由非特异性细胞如其他B细胞、巨噬细胞或树突状细胞完成。