Kawano M, Iwato K, Kuramoto A
J Immunol. 1985 Jan;134(1):375-81.
The culture supernatants of Con A-activated human peripheral blood mononuclear cells (PBM) contained at least two regulatory factors upon B cell proliferation. One was B cell growth factor (BCGF), which activated antigen-stimulated B cells to proliferation and clonal expansion, and the other was its inhibitory factor, arbitrarily named B cell growth inhibitory factor (BIF). This BIF inhibited the effect of BCGF on anti-mu-stimulated B cells or the monoclonal mature B cell line (CLL-T.H.) obtained from the peripheral blood lymphocytes of B cell-type chronic lymphocytic leukemia patients, which were activated only with BCGF and without adding other proliferating stimuli (e.g., anti-mu). BIF activity was detected in the 24 hr culture supernatants of Con A-activated human PBM in FCS containing medium and also in serum-free RPMI 1640 medium. This substance with BIF activity could not be derived from FCS. Con A-induced BIF (m.w. of 80,000 and an isoelectric point of pH 5.4) was analyzed by Sephadex G-200 gel filtration and chromatofocusing. BIF was stable at pH 2.0 and at 56 degrees C for 30 min. Partially purified BIF had no effect on cell viability and almost no interferon activity (less than 1 IU/ml). BIF with high titer had a slight but significant inhibition on TCGF-dependent T cell growth and on PHA or Con A responses, but the extent of these inhibitions was far less than that of BCGF-dependent B cell growth. Absorption of BIF with Con A blasts made its inhibition on T cell growth even less. On the other hand, BIF activity could not be absorbed with Con A blasts but was almost absorbed with large numbers of CLL-T.H. cells. BIF had almost no inhibitory effect on the proliferation of a mouse fibroblast cell line (NIH 3T3), a mouse myeloma cell line (NS-1), human lymphoid cell lines (MOLT-4, HSB-2, and Daudi), or a human myeloid cell line (K-562). BIF-producing cells were estimated to be T cells and were identified as T8+ T cells. On the other hand, Con A-induced BCGF was demonstrated to be produced predominantly by T4+ T cells. These results show that human B cell proliferation is regulated by interaction between T4+ and T8+ cells via soluble factors, namely BCGF and BIF, respectively.
刀豆蛋白A激活的人外周血单个核细胞（PBM）的培养上清液中含有至少两种调节B细胞增殖的因子。一种是B细胞生长因子（BCGF），它能激活抗原刺激的B细胞进行增殖和克隆扩增，另一种是其抑制因子，暂命名为B细胞生长抑制因子（BIF）。这种BIF可抑制BCGF对抗μ刺激的B细胞或从B细胞型慢性淋巴细胞白血病患者外周血淋巴细胞中获得的单克隆成熟B细胞系（CLL-T.H.）的作用，这些细胞仅用BCGF激活，不添加其他增殖刺激物（如抗μ）。在含有胎牛血清（FCS）的培养基以及无血清的RPMI 1640培养基中，均可在刀豆蛋白A激活的人PBM的24小时培养上清液中检测到BIF活性。这种具有BIF活性的物质并非来源于FCS。通过Sephadex G-200凝胶过滤和色谱聚焦分析了刀豆蛋白A诱导产生的BIF（分子量为80,000，等电点为pH 5.4）。BIF在pH 2.0和56℃下30分钟内稳定。部分纯化的BIF对细胞活力无影响，且几乎无干扰素活性（小于1 IU/ml）。高滴度的BIF对依赖TCGF的T细胞生长以及对PHA或刀豆蛋白A的反应有轻微但显著的抑制作用，但其抑制程度远小于依赖BCGF的B细胞生长。用刀豆蛋白A刺激的母细胞吸附BIF后，其对T细胞生长的抑制作用更小。另一方面，BIF活性不能被刀豆蛋白A刺激的母细胞吸附，但几乎可被大量的CLL-T.H.细胞吸附。BIF对小鼠成纤维细胞系（NIH 3T3）、小鼠骨髓瘤细胞系（NS-1）、人淋巴细胞系（MOLT-4、HSB-2和Daudi）或人髓细胞系（K-562）的增殖几乎无抑制作用。产生BIF的细胞估计为T细胞，并被鉴定为T8 + T细胞。另一方面，已证明刀豆蛋白A诱导产生的BCGF主要由T4 + T细胞产生。这些结果表明，人B细胞增殖是通过T4 +和T8 +细胞之间分别经由可溶性因子BCGF和BIF的相互作用来调节的。
