Characterization of antigen processing and presentation by resting B lymphocytes.
Characterization of antigen processing and presentation by resting B lymphocytes.
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DOI：
10.4049/jimmunol.140.5.1408
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发表时间：
1988-03
影响因子：
4.4
通讯作者：
E. Gosselin;H. Tony;D. Parker
中科院分区：
文献类型：
--
作者：
E. Gosselin;H. Tony;D. Parker
胸腺依赖性Ag抗体的产生需要B细胞和Ag特异性Th细胞之间的合作。这种相互作用的MHC限制意味着Th细胞在MHC分子的背景下识别B细胞表面上的Ag，并且Ag特异性B细胞通过充当Th细胞的APC而获得帮助。然而，许多研究表明，正常的静息B细胞作为APC是无效的，这意味着B细胞必须离开静息状态才能与Th细胞特异性相互作用。其他研究，包括我们自己的兔球蛋白特异性小鼠T细胞系和杂交瘤，表明某些T细胞系可以有效地刺激正常的静息B细胞。对上述矛盾的一种可能解释是，我们的B细胞在呈递前就已被激活。在这里，我们表明，大小选择的小B细胞的介绍是不是由T细胞或培养基的成分产生的非特异性激活信号的结果。此外，虽然LPS活化确实增加了小B细胞的呈递效率，但用大细胞代替小细胞或用促有丝分裂剂量的抗Ig预孵育静息B细胞并不能。我们考虑的另一种可能性是小B细胞不能处理Ag，我们选择了能够识别B细胞表面天然Ag的T细胞系。在大多数情况下，用B细胞系和巨噬细胞进行的实验表明，Ag呈递需要Ag加工，这是一系列事件，包括Ag内化到酸室中，Ag变性或消化成片段，以及在II类MHC分子的背景下Ag返回到细胞表面。这里报道的实验表明，我们的T细胞系需要一个Ag加工步骤，并且小的静息B细胞，像其他APC一样，在将Ag呈递给T细胞之前加工Ag。具体而言，我们表明，2至4小时的孵育后，银脉冲前银介绍变得耐辐照。在脉冲后不久，Ag进入链霉蛋白酶抗性隔室。尽管有效的Ag呈递需要最初与膜IG结合，但Ag在呈递时不再与膜IG结合，并且不以其完整形式呈递，因为山羊抗IG去除膜IG阻断了Ag脉冲之前而非之后的呈递。
The production of antibody to a thymus-dependent Ag requires cooperation between the B cell and an Ag-specific Th cell. MHC restriction of this interaction implies that the Th cell recognizes Ag on the B cell surface in the context of MHC molecules and that the Ag-specific B cell gets help by acting as an APC for the Th cell. However, a number of studies have suggested that normal resting B cells are ineffective as APC, implying that the B cell must leave the resting state before it can interact specifically with a Th cell. Other studies, including our own with rabbit globulin-specific mouse T cell lines and hybridomas, show that certain T cell lines can be efficiently stimulated by normal resting B cells. One possible explanation for the above contradiction is that our B cells have become activated before presentation. Here we show that presentation by size-selected small B cells is not the result of nonspecific activation signals generated by the T cells or components of the medium. Also, although LPS activation does increase the efficiency of presentation by small B cells, use of large cells in place of small cells or preincubation of resting B cells with mitogenic doses of anti-Ig does not. Another possibility that we considered was that small B cells are unable to process Ag and that we had selected T cell lines that were capable of recognizing native Ag on the B cell surface. In the majority of cases, experiments with B cell lines and macrophages have shown that Ag presentation requires Ag processing, a sequence of events that includes internalization of Ag into an acid compartment, denaturation or digestion of Ag into fragments, and its return to the cell surface in the context of class II MHC molecules. The experiments reported here show that our T cell lines require an Ag processing step and that small resting B cells, like other APC, process Ag before presenting it to T cells. Specifically, we show that an incubation of 2 to 4 h is required after the Ag pulse before Ag presentation becomes resistant to irradiation. Shortly after the pulse, the Ag enters a pronase-resistant compartment. Although efficient Ag presentation requires initial binding to membrane Ig, Ag is no longer associated with membrane Ig at the time of presentation and is not presented in its intact form, because removal of membrane Ig by goat anti-Ig blocks presentation before but not after the Ag pulse.