Rudensky A Y, Yurin V L
Laboratory of Immunology, All-Union Research Institute for Genetics, Moscow, USSR.
Eur J Immunol. 1989 Sep;19(9):1677-83. doi: 10.1002/eji.1830190923.
Immunoglobulin (Ig)-specific T-B cell interactions have been studied in the model of T cell recognition of the kappa chain Ig kappa-1b allotype in Ig kappa-1-congeneic rat strains. An efficient presentation of endogenous Ig allotypic determinants by irradiated spleen cells from (WAG.1b x August)F1 (RT-1u/c; Ig kappa-1b/1a) rats to Ig kappa-1b-specific lymph node T cells from Ig kappa-1-congeneic (WAG x August)F1 (RT-1u/c; Ig kappa-1a) rats was demonstrated. This presentation was found to be sensitive to high irradiation doses (greater than 1000 rad). By fractionation of Ig kappa-1b+ F1 spleen cells on Percoll density gradient we have shown that a radioresistant, low-density fraction, consisting mainly of macrophages (M phi) and dendritic cells, triggers only weak Ig kappa-1b-specific T cell response. The high level of response was observed against radiosensitive spleen cell fractions of intermediate and high density, suggesting that B cells were the main antigen-presenting cells (APC) of Ig kappa-1b determinants of endogenous Ig. This conclusion was confirmed in the experiments using purified B cells from Ig kappa-1b-bearing rats. Earlier we have shown that the responsiveness of August (RT-1c; Ig kappa-1a) and WAG (RT-1u; Ig kappa-1a) rats to Ig kappa-1b in vivo is controlled by the dominant allele of an RT-1-linked Ir gene. August and (August X WAG)F1 rats were found to be responders to Ig kappa-1b while WAG rats were nonresponders. The same pattern of Ir gene-controlled reactivity was demonstrated using an Ig kappa-1b-specific T cell proliferation assay. Ig kappa-1b-specific F1 T cell response was only observed when Ig kappa-1b+ B cells or IgG (Ig kappa-1b)-pulsed M phi-bearing responder major histocompatibility complex (MHC) haplotype were used as the APC. Anti-RT-1 monoclonal antibody inhibition studies suggested that the RT-1Bc molecule is the main restricting element of T cell recognition of Ig kappa-1b+ B cell as well as exogenous IgG (Ig kappa-1b). We have demonstrated allelic exclusion of Ig kappa-1b presenting function by negatively and positively selecting for Ig kappa-1b+ and Ig kappa-1a+ B cells from heterozygous F1(Ig kappa-1b/1a) rats. This clearly indicate that the B cells presented exclusively Ig kappa-1b allotypic determinants of their own Ig.(ABSTRACT TRUNCATED AT 400 WORDS)
免疫球蛋白(Ig)特异性T细胞与B细胞的相互作用已在Igκ-1同基因大鼠品系中κ链Igκ-1b同种异型的T细胞识别模型中进行了研究。已证明,(WAG.1b×奥古斯特)F1(RT-1u/c;Igκ-1b/1a)大鼠经照射的脾细胞能有效地将内源性Ig同种异型决定簇呈递给来自Igκ-1同基因(WAG×奥古斯特)F1(RT-1u/c;Igκ-1a)大鼠的Igκ-1b特异性淋巴结T细胞。发现这种呈递对高辐射剂量(大于1000拉德)敏感。通过在Percoll密度梯度上对Igκ-1b + F1脾细胞进行分级分离,我们发现主要由巨噬细胞(M phi)和树突状细胞组成的抗辐射低密度级分仅引发微弱的Igκ-1b特异性T细胞反应。观察到针对中密度和高密度的辐射敏感脾细胞级分有高水平反应,这表明B细胞是内源性Ig的Igκ-1b决定簇的主要抗原呈递细胞(APC)。使用来自携带Igκ-1b大鼠的纯化B细胞进行的实验证实了这一结论。早些时候我们已表明,奥古斯特(RT-1c;Igκ-1a)和WAG(RT-1u;Igκ-1a)大鼠在体内对Igκ-1b的反应性受RT-1连锁Ir基因的显性等位基因控制。发现奥古斯特和(奥古斯特×WAG)F1大鼠对Igκ-1b有反应,而WAG大鼠无反应。使用Igκ-1b特异性T细胞增殖试验也证明了相同模式的Ir基因控制的反应性。仅当使用Igκ-1b + B细胞或携带IgG(Igκ-1b)脉冲的M phi的反应性主要组织相容性复合体(MHC)单倍型作为APC时,才观察到Igκ-1b特异性F1 T细胞反应。抗RT-1单克隆抗体抑制研究表明,RT-1Bc分子是T细胞识别Igκ-1b + B细胞以及外源性IgG(Igκ-1b)的主要限制元件。我们通过从杂合F1(Igκ-1b/1a)大鼠中对Igκ-1b +和Igκ-1a + B细胞进行阴性和阳性选择,证明了Igκ-1b呈递功能的等位基因排斥。这清楚地表明,B细胞仅呈递其自身Ig的Igκ-1b同种异型决定簇。(摘要截断于400字)