Ralph P, Jeong G, Welte K, Mertelsmann R, Rabin H, Henderson L E, Souza L M, Boone T C, Robb R J
J Immunol. 1984 Nov;133(5):2442-5.
In certain human IgM and IgG cell lines, immunoglobulin (Ig) secretion is highly stimulated by a B cell inducing factor (BIF) that is free of interleukin 2 (IL 2). BIF also induces Ig secretion in purified peripheral blood B cell populations that have been mitogenically stimulated by Staphylococcus aureus bacteria. Low concentrations of IL 2 (less than 20 U/ml) are not active in these systems. We now show that IL 2 at concentrations above 100 U/ml can induce Ig secretion in these blood B cells and B cell lines. Both conventional IL 2, purified from the human JURKAT and gibbon MLA-144 cell lines, and recombinant IL 2 are active. Very high concentrations approaching 10(4) U/ml are optimal for Ig secretion. Antibody to the T cell IL 2 receptor, anti-Tac, did not inhibit stimulation of the IgM cell line SKW6.4 by IL 2, and no Tac antigen was detected on the cells. The 9B11 monoclonal anti-IL 2 antibody that neutralizes T cell growth activity also abrogates stimulation of Ig secretion by conventional and recombinant IL 2 in the SKW6.4 cell line. However, the 1H11 monoclonal anti-(conventional thr3-glycosylated IL 2), which does not neutralize T cell growth activity, does inhibit induction of Ig secretion by the corresponding IL 2 in the B cell line. These results suggest that IL 2 stimulates B cells via a low-affinity interaction with a receptor different from the Tac receptor identified on T cells, and that the active site on the IL 2 molecule for B cells differs from that for T cell targets. If IL 2 promotes Ig secretion by binding with a low affinity to the B cell BIF receptor, IL 2 and BIF could be homologous proteins.
在某些人IgM和IgG细胞系中,免疫球蛋白(Ig)分泌受到一种不含白细胞介素2(IL-2)的B细胞诱导因子(BIF)的强烈刺激。BIF还能在经金黄色葡萄球菌有丝分裂原刺激的纯化外周血B细胞群体中诱导Ig分泌。低浓度的IL-2(低于20 U/ml)在这些系统中无活性。我们现在发现,浓度高于100 U/ml的IL-2能在这些血液B细胞和B细胞系中诱导Ig分泌。从人JURKAT和长臂猿MLA-144细胞系中纯化的传统IL-2以及重组IL-2均具有活性。接近10⁴ U/ml的非常高浓度对Ig分泌最为适宜。针对T细胞IL-2受体的抗体抗-Tac,并不抑制IL-2对IgM细胞系SKW6.4的刺激,且在这些细胞上未检测到Tac抗原。能中和T细胞生长活性的9B11单克隆抗-IL-2抗体,也能消除传统和重组IL-2对SKW6.4细胞系中Ig分泌的刺激。然而,不中和T细胞生长活性的1H11单克隆抗-(传统苏氨酸³-糖基化IL-2),确实能抑制相应IL-2对B细胞系中Ig分泌的诱导。这些结果表明,IL-2通过与一种不同于在T细胞上鉴定出的Tac受体的受体进行低亲和力相互作用来刺激B细胞,并且IL-2分子上针对B细胞的活性位点不同于针对T细胞靶标的活性位点。如果IL-2通过与B细胞BIF受体低亲和力结合来促进Ig分泌,那么IL-2和BIF可能是同源蛋白。