CAPACITY OF ANTIGEN UPTAKE BY B-CELLS, FIBROBLASTS OR MACROPHAGES DETERMINES EFFICIENCY OF PRESENTATION OF A SOLUBLE SELF ANTIGEN (C5) TO LYMPHOCYTES-T
CAPACITY OF ANTIGEN UPTAKE BY B-CELLS, FIBROBLASTS OR MACROPHAGES DETERMINES EFFICIENCY OF PRESENTATION OF A SOLUBLE SELF ANTIGEN (C5) TO LYMPHOCYTES-T
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DOI：
10.1002/eji.1830220523
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发表时间：
1992-05-01
影响因子：
5.4
通讯作者：
STOCKINGER, B
中科院分区：
文献类型：
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作者：
STOCKINGER, B
体液中的自身抗原必须被抗原呈递细胞 (APC) 吸收、加工和呈递，以诱导 T 细胞耐受。对于自身抗原，如补体的第五种成分 (C5)，APC 不会通过抗原特异性受体摄取，呈递必须依赖于非特异性方式的摄取。 C5 被用作可溶性自身抗原模型，以研究不同 APC（B 淋巴瘤细胞、成纤维细胞和巨噬细胞）摄取、加工和呈递低浓度可溶性 C5 至 C5 特异性 T 细胞杂交体的能力。在限制抗原量的条件下，巨噬细胞和成纤维细胞表现出相似的可溶性 C5 呈递能力，而 B 细胞则不然。在 C5 特异性抗体存在的情况下，巨噬细胞的 C5 呈递得到增强，如果以颗粒乳胶-抗原-抗体复合物的形式添加抗原，则进一步增强，表明通过 Fc 受体介导的内吞作用或吞噬作用增强了摄取。仅当 C5 特异性抗体存在时，B 细胞才会呈现可溶性 C5。在这些条件下，C5 的摄取是通过 II 型 Fc 受体发生的。这种抗原摄取途径不适用于非特异性内吞作用后有效呈递的其他抗原。根据这些发现，似乎可以合理地提出，B 细胞对 C5 等血清蛋白的非特异性内吞作用通常受到限制，以避免干扰它们在抗原受体介导的摄取和呈递以启动抗体反应中的关键作用。根据抗原的物理形状，循环中存在的可溶性自身抗原的呈递通常可能是树突细胞和巨噬细胞的任务。
Self antigens in the body fluids must be taken up, processed and presented by antigen-presenting cells (APC) in order to induce T cell tolerance. For self antigens like the fifth component of complement (C5) which is not picked up by APC via antigen-specific receptors, presentation has to rely on uptake by nonspecific means. C5 was used as a model soluble self antigen to study the capacity of different APC (B lymphoma cells, fibroblasts and macrophages) of taking up, processing and presenting low concentrations of soluble C5 to C5 specific T cell hybrids. Under conditions of limiting antigen amounts macrophages and fibroblasts exhibited similar presentation capacity for soluble C5 while B cells did not. C5 presentation by macrophages was enhanced in the presence of C5-specific antibody and augmented further if antigen was added in the form of particulate latex-antigen-antibody complexes indicating enhanced uptake via Fc receptor-mediated endocytosis or phagocytosis. B cells presented soluble C5 only in the presence of C5-specific antibody. Uptake of C5 under these conditions occurred via Fc receptors type II. This pathway of antigen uptake did not operate with other antigens which were presented efficiently after nonspecific endocytosis.In light of these findings it seems reasonable to propose that nonspecific endocytosis of serum proteins like C5 by B cells is normally limited in order to avoid interference with their critical role in antigen receptor-mediated uptake and presentation for the initiation of an antibody response. It seems likely that presentation of soluble self antigens present in the circulation may normally be the task of dendritic cells and macrophages depending on the physical shape of the antigen.