Armitage R J, Macduff B M, Spriggs M K, Fanslow W C
Department of Immunology, Immunex Research and Development Corporation, Seattle, WA 98101.
J Immunol. 1993 May 1;150(9):3671-80.
Recombinant human CD40 ligand (hCD40L) was expressed on the surface of CV1/EBNA cells and examined for its ability to induce proliferation and Ig secretion from human B cells in the presence or absence of soluble cytokines. hCD40L was directly mitogenic in a dose-dependent fashion for purified tonsil B cells with maximal proliferation occurring at days 5 to 7. Proliferation induced by CD40L was significantly enhanced in the presence of IL-2, IL-4, or IL-10 and strongly suppressed by transforming growth factor-beta. Although IL-5, TNF-alpha, and IFN-gamma had no stimulatory effect in the presence of hCD40L alone, if IL-4 was also present in cultures, these cytokines enhanced the proliferative response above that seen with IL-4 alone. Interestingly, in the absence of IL-4, IFN gamma had an inhibitory effect on hCD40L-induced proliferation. Although CD40L alone did not enhance Ig secretion, addition of IL-2 or IL-10 to the cultures significantly elevated the levels of IgM, IgG1, and IgA that were observed. Addition of IL-4 to the cultures did not enhance secretion of these isotypes but had a weak inhibitory effect. However, CD40L-mediated induction of IgG4 and IgE was dependent on the presence of IL-4. Of the cytokines examined, only IL-10 enhanced IgE secretion under these conditions. Although transforming growth factor-beta only partially inhibited secretion of IgM, IgG1, and IgA, it was strongly suppressive for IgG4 and IgE production. Our data demonstrate that proliferation and Ig secretion induced in the presence of CD40L can be modulated in a positive and negative fashion by soluble cytokines. IL-2 and IL-10 specifically enhance IgM, IgG1, and IgA production although IL-4, despite costimulating B cell proliferation, does not augment secretion of these isotypes but provided an essential cosignal with CD40L for the production of IgG4 and IgE.
重组人CD40配体（hCD40L）在CV1/EBNA细胞表面表达，并在有或没有可溶性细胞因子存在的情况下检测其诱导人B细胞增殖和分泌免疫球蛋白的能力。hCD40L以剂量依赖方式对纯化的扁桃体B细胞具有直接促有丝分裂作用，在第5至7天出现最大增殖。在存在白细胞介素-2（IL-2）、白细胞介素-4（IL-4）或白细胞介素-10（IL-10）的情况下，CD40L诱导的增殖显著增强，而转化生长因子-β（TGF-β）则强烈抑制增殖。尽管单独存在hCD40L时，IL-5、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）没有刺激作用，但如果培养物中也存在IL-4，这些细胞因子会增强增殖反应，使其高于单独使用IL-4时的水平。有趣的是，在没有IL-4的情况下，IFN-γ对hCD40L诱导的增殖有抑制作用。尽管单独的CD40L不会增强免疫球蛋白分泌，但向培养物中添加IL-2或IL-10会显著提高观察到的IgM、IgG1和IgA水平。向培养物中添加IL-4不会增强这些同种型的分泌，但有微弱的抑制作用。然而，CD40L介导的IgG4和IgE诱导依赖于IL-4的存在。在检测的细胞因子中，只有IL-10在这些条件下增强IgE分泌。尽管TGF-β仅部分抑制IgM、IgG1和IgA的分泌，但它对IgG4和IgE的产生有强烈抑制作用。我们的数据表明，在CD40L存在的情况下诱导的增殖和免疫球蛋白分泌可被可溶性细胞因子以正负两种方式调节。IL-2和IL-10特异性增强IgM、IgG1和IgA的产生，尽管IL-4共同刺激B细胞增殖，但不会增加这些同种型的分泌，但为产生IgG4和IgE提供了与CD40L的必需共信号。
