Fanslow W C, Anderson D M, Grabstein K H, Clark E A, Cosman D, Armitage R J
Department of Immunology, Immunex Research and Development Corporation, Seattle, WA 98101.
J Immunol. 1992 Jul 15;149(2):655-60.
We have expressed the CD40 surface Ag as both a soluble 28-kDa molecule and a 57-kDa Fc fusion protein containing the human IgG1 Fc region. Soluble CD40 and the Fc fusion protein inhibited the proliferative response of anti-IgM-activated human B cells to the CD40 mAb G28-5. Similarly, G28-5- and IL-4-induced IgE secretion from PBMC depleted of T cells was effectively blocked by both forms of soluble CD40. Although the soluble constructs of CD40 had only a minimal inhibitory effect on IL-4-mediated proliferation of anti-IgM-activated B cells, IL-4-induced soluble CD23 shedding from both PBMC and T cells depleted of PBMC, and IgE secretion from PBMC, were significantly reduced in a concentration-dependent manner when soluble CD40 was present in the culture. The data presented demonstrate that both soluble forms of the CD40 molecule are biologically active, and suggest that the ligand for CD40 is inducible in IL-4-stimulated cultures and that it mediates both shedding of sCD23 and IgE secretion.
我们已将CD40表面抗原表达为一种28 kDa的可溶性分子和一种含有人类IgG1 Fc区域的57 kDa Fc融合蛋白。可溶性CD40和Fc融合蛋白抑制了抗IgM激活的人B细胞对CD40单克隆抗体G28-5的增殖反应。同样，G28-5和IL-4诱导的来自T细胞耗竭的PBMC的IgE分泌被两种形式的可溶性CD40有效阻断。尽管CD40的可溶性构建体对抗IgM激活的B细胞的IL-4介导的增殖仅有最小的抑制作用，但当培养物中存在可溶性CD40时，IL-4诱导的来自PBMC和PBMC耗竭的T细胞的可溶性CD23脱落以及来自PBMC的IgE分泌以浓度依赖的方式显著降低。所呈现的数据表明，CD40分子的两种可溶性形式均具有生物活性，并表明CD40的配体在IL-4刺激的培养物中是可诱导的，并且它介导sCD23的脱落和IgE分泌。
