Beagley K W, Eldridge J H, Kiyono H, Everson M P, Koopman W J, Honjo T, McGhee J R
Department of Microbiology, University of Alabama, Birmingham, AL 35294.
J Immunol. 1988 Sep 15;141(6):2035-42.
Recent studies have shown that purified IL-5 from T cell lines and clones enhances IgA synthesis in LPS-triggered splenic B cell cultures, and that this effect is augmented by IL-4. In this study we have examined the ability of rIL-5 and rIL-4 to support spontaneous Ig synthesis in normal Peyer's patch (PP) B cell cultures. The rIL-4 supported proliferation of the HT-2 and in vivo adapted BCL-1 cell lines, increased Ia expression on normal spleen B cells, co-stimulated splenic B cell proliferation in the presence of anti-mu and enhanced IgG1 synthesis in LPS triggered splenic B cell cultures. The rIL-5 supported BCL-1 proliferation, co-stimulated splenic B cell proliferation in the presence of dextran sulfate, and increased IgA synthesis in LPS-stimulated splenic B cell cultures. Markedly enhanced IgA responses occurred in PP B cell, but not splenic B cell cultures supplemented with rIL-5 in the absence of an added B cell trigger. However, rIL-4 alone did not enhance IgA synthesis or increase the IgA synthesis of PP B cell cultures stimulated with rIL-5. The rIL-5 receptive PP B cells were present in the blast cell subpopulation, inasmuch as a low density fraction isolated on Percoll gradients accounted for the enhanced IgA synthesis. Further, cell cycle analysis of whole PP B cells using propidium iodide in conjunction with staining for surface B220, demonstrated that approximately 12 to 16% of the B cells were in the S and G2/M stages of cell cycle, the remainder being in Go + G1. The surface IgM+ B cells were predominantly in Go + G1, whereas the sIgA+ B cell subpopulation was enriched for cells in the S and G2/M compartments. The PP B cell subset responsible for enhanced IgA synthesis in the presence of rIL-5 was sIgA-positive because FACS-depletion of the sIgA+ B cells resulted in the total loss of rIL-5 enhanced IgA synthesis. Further, when PP B cells were enriched for sIgA+ B cells by cell sorting, these cells responded to rIL-5 with increased IgA synthesis in a dose-dependent manner. When the actual numbers of IgA secreting cells were assessed in PP B cell cultures with supplemental rIL-5, no significant increase in total IgA-producing cells was noted when compared with B cells cultured without rIL-5.(ABSTRACT TRUNCATED AT 400 WORDS)
近期研究表明，从T细胞系和克隆体中纯化得到的白细胞介素-5（IL-5）可增强脂多糖（LPS）触发的脾B细胞培养物中的IgA合成，且白细胞介素-4（IL-4）可增强此效应。在本研究中，我们检测了重组白细胞介素-5（rIL-5）和重组白细胞介素-4（rIL-4）在正常派伊尔结（PP）B细胞培养物中支持自发Ig合成的能力。rIL-4可支持HT-2和体内适应性BCL-1细胞系的增殖，增加正常脾B细胞上Ia的表达，在抗μ存在的情况下共刺激脾B细胞增殖，并增强LPS触发的脾B细胞培养物中的IgG1合成。rIL-5可支持BCL-1增殖，在硫酸葡聚糖存在的情况下共刺激脾B细胞增殖，并增加LPS刺激的脾B细胞培养物中的IgA合成。在未添加B细胞触发剂的情况下，补充rIL-5的PP B细胞培养物中出现了明显增强的IgA反应，但脾B细胞培养物中未出现。然而，单独的rIL-4并不能增强IgA合成，也不能增加用rIL-5刺激的PP B细胞培养物中的IgA合成。rIL-5反应性PP B细胞存在于母细胞亚群中，因为通过Percoll梯度分离的低密度部分导致了IgA合成增强。此外，使用碘化丙啶结合表面B220染色对整个PP B细胞进行细胞周期分析表明，约12%至16%的B细胞处于细胞周期的S期和G2/M期，其余细胞处于G0+G1期。表面IgM+B细胞主要处于G0+G1期，而sIgA+B细胞亚群在S期和G2/M区室中的细胞富集。在存在rIL-5的情况下负责增强IgA合成的PP B细胞亚群是sIgA阳性的，因为sIgA+B细胞的荧光激活细胞分选（FACS）去除导致rIL-5增强的IgA合成完全丧失。此外，当通过细胞分选富集PP B细胞中的sIgA+B细胞时，这些细胞对rIL-5的反应是IgA合成以剂量依赖性方式增加。当在补充rIL-5的PP B细胞培养物中评估IgA分泌细胞的实际数量时，与未培养rIL-5的B细胞相比，未观察到总IgA产生细胞有显著增加。（摘要截短至400字）
