Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliferation.
Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliferation.
复制标题
皮克量的抗 Ig 抗体与葡聚糖偶联可诱导 B 细胞增殖。
作者：
M. Brunswick;F. Finkelman;P. Highet;J. Inman;H. Dintzis;James J. Mond
为了研究能够使2型Ag（如右旋糖酐和Ficoll所例示）在相对不存在T细胞的情况下刺激高水平抗体应答的性质，我们将抗IgD和抗IgM mAb与右旋糖酐和Ficoll两者缀合，并检查它们的B细胞活化性质。这种缀合的抗Ig抗体在皮克浓度下刺激B细胞活化的早期和晚期，所述皮克浓度比未缀合的抗Ig抗体刺激B细胞所需的浓度低至少1000倍，并且它们刺激的增殖水平平均高10倍。此外，调节来自B细胞表面的小sIgD的抗Ig葡聚糖浓度（100 pg/ml）是增强的B细胞MHC II类分子表达的强诱导剂。抗IgD或非促有丝分裂抗IgM mAb的Fab片段与葡聚糖的缀合使得它们与缀合至强刺激性抗IgD或抗IgM抗体的葡聚糖一样促有丝分裂。葡聚糖和Ficoll作为抗IgD有效载体分子的能力不仅仅与它们的大分子量有关，因为抗IgD偶联到聚合的BSA（m.w. 1.5 X 10（6），在刺激B细胞DNA合成方面仅比未结合的抗IgD抗体强10- 50倍。因此，这些结果表明，皮克浓度的半抗原化的2型Ag刺激IG分泌的独特能力，在T细胞的情况下，可能是一个功能，他们的能力，以促进有效的交联，而不会导致调制的sIG。这将使这种Ag能够介导重复的B细胞信号传导，这是通过未缀合的抗Ig抗体不能实现的情况，所述未缀合的抗Ig抗体导致在其促有丝分裂浓度下调节sIg。因此，这些化合物可用于研究由sIg交联刺激的B细胞活化，所述sIg交联的浓度可更接近地反映在生理条件下由2型Ag实现的那些。
To investigate the properties which enable type 2 Ag, as exemplified by dextran and Ficoll, to stimulate high levels of antibody responses in the relative absence of T cells, we conjugated anti-IgD and anti-IgM mAb to both dextran and Ficoll and examined their B cell-activating properties. Such conjugated anti-Ig antibodies stimulated both early and later stages of B cell activation at picogram concentrations, which are at least 1000-fold lower than that required for B cell stimulation by unconjugated anti-Ig antibodies, and the level of proliferation they stimulated was on average 10-fold greater. Furthermore, concentrations of anti-Ig dextran (100 pg/ml) which modulated little sIgD from the B cell surface were strong inducers of enhanced B cell expression of MHC class II molecules. Conjugation of Fab fragments of anti-IgD or nonmitogenic anti-IgM mAb to dextran rendered them as mitogenic as dextran conjugated to strongly stimulatory anti-IgD or anti-IgM antibodies. The ability of dextran and Ficoll to serve as effective carrier molecules for anti-IgD was not related solely to their large m.w., because anti-IgD coupled to polymerized BSA (m.w. 1.5 X 10(6), was only 10- to 50-fold more potent than unconjugated anti-IgD antibodies at stimulating B cell DNA synthesis. These results suggest, therefore, that the unique ability of picogram concentrations of haptenated type 2 Ag to stimulate Ig secretion in the absence of T cells may be a function of their ability to promote effective cross-linking without resulting in the modulation of sIg. This would enable such Ag to mediate repetitive B cell signaling, a situation that cannot be achieved by unconjugated anti-Ig antibodies which result in modulation of sIg at their mitogenic concentrations. These compounds therefore may be employed to study B cell activation stimulated by sIg cross-linking at concentrations that may more closely reflect those which are achieved under physiologic conditions by type 2 Ag.