In vitro and in vivo B lymphocyte-activating properties of monoclonal anti-delta antibodies. I. Determinants of B lymphocyte-activating properties.
In vitro and in vivo B lymphocyte-activating properties of monoclonal anti-delta antibodies. I. Determinants of B lymphocyte-activating properties.
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DOI：
10.4049/jimmunol.136.7.2382
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发表时间：
1986-04
影响因子：
4.4
通讯作者：
D. K. Goroff;A. Stall;J. Mond;F. Finkelman
中科院分区：
文献类型：
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作者：
D. K. Goroff;A. Stall;J. Mond;F. Finkelman
为了更好地理解B淋巴细胞被抗Ig抗体激活的机制，我们表征了7种单克隆小鼠同种异型IgD抗体的同种型、精细特异性、IgD交联能力、亲合力以及在体外和体内激活B细胞的能力。测试的三种单克隆抗体以相对高的亲合力与IgD的Fc片段结合，并且在交联IgD方面是有效的，因为它们沉淀可溶性IgD并且快速地将B细胞膜IgD加帽。这些是唯一测试的在体外诱导B细胞DNA合成的抗体，并且是在体内诱导B细胞大小和DNA合成增加以及在体外和体内诱导B细胞表面Ia表达增加的最有效抗体。两种抗体以相对高的亲合力结合IgD的Fd片段，但即使在2%聚乙二醇的存在下也不能快速地帽合细胞膜IgD或沉淀可溶性IgD。这些高亲合力、低交联性的抗体不能刺激体外B细胞DNA合成，并且在刺激体内B细胞DNA合成、大小或表面Ia表达增加或体外表面Ia表达增加方面比第一组抗δ抗体的有效性低得多。一种抗体以中等亲合力与IgD的Fc片段结合，不能快速加帽于B细胞膜IgD或在盐水中沉淀可溶性IgD，但在2%聚乙二醇存在下可以沉淀可溶性IgD。该抗体在体外不能诱导B细胞DNA合成，并且在刺激B细胞大小、表面Ia表达和体内DNA合成以及体外表面Ia表达的增加方面与较高亲合力、较差交联的抗体一样有效。一种抗体以低亲合力与IgD的Fd片段结合，并且不能沉淀可溶性IgD或覆盖细胞膜IgD，通过所研究的任何参数几乎没有激活B细胞的能力。每种单克隆抗δ抗体，无论同种型或精细特异性如何，当与琼脂糖结合以增加其交联IgD的能力时，在体外对B细胞具有促有丝分裂作用。抗a同种异型IgD的单克隆抗体在体外或体内均不能刺激来自B同种异型小鼠的B细胞增加其大小、表面Ia表达或DNA合成。（400字处删节）
To appreciate better the mechanisms by which B lymphocytes are activated by anti-Ig antibodies, we characterized seven monoclonal mouse allo-antibodies to IgD of the a allotype for their isotypes, fine specificities, IgD-cross-linking abilities, avidities, and abilities to activate B cells in vitro and in vivo. Three of the monoclonal antibodies tested bound to the Fc fragment of IgD with relatively high avidity and were effective at cross-linking IgD, since they precipitated soluble IgD and rapidly capped B cell membrane IgD. These were the only antibodies tested that induced B cell DNA synthesis in vitro and were the most effective antibodies at inducing in vivo increases in B cell size and DNA synthesis and in vitro and in vivo increases in B cell surface Ia expression. Two antibodies bound to the Fd fragment of IgD with relatively high avidity but could not rapidly cap cell membrane IgD or precipitate soluble IgD even in the presence of 2% polyethylene glycol. These high-avidity, poorly cross-linking antibodies were unable to stimulate B cell DNA synthesis in vitro and were much less effective than the first group of anti-delta antibodies at stimulating in vivo increases in B cell DNA synthesis, size, or surface Ia expression or in vitro increases in surface Ia expression. One antibody, which bound to the Fc fragment of IgD with an intermediate avidity, was unable to rapidly cap B cell membrane IgD or precipitate soluble IgD in saline, but could precipitate soluble IgD in the presence of 2% polyethylene glycol. This antibody failed to induce B cell DNA synthesis in vitro and was as effective as the higher-avidity, poorly cross-linking antibodies at stimulating increases in B cell size, surface Ia expression, and DNA synthesis in vivo, and surface Ia expression in vitro. One antibody, which bound to the Fd fragment of IgD with low avidity and was unable to precipitate soluble IgD or to cap cell membrane IgD, had little ability to activate B cells by any of the parameters studied. Each of the monoclonal anti-delta antibodies, regardless of isotype or fine specificity, when bound to agarose to increase its ability to cross-link IgD, was mitogenic for B cells in vitro. None of the monoclonal antibodies to IgD of the a allotype stimulated B cells from b allotype mice to increase their size, surface Ia expression, or synthesis of DNA in vitro or in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)