Holder M J, Liu Y J, Defrance T, Flores-Romo L, MacLennan I C, Gordon J
Department of Immunology, Medical School, Birmingham, UK.
Int Immunol. 1991 Dec;3(12):1243-51. doi: 10.1093/intimm/3.12.1243.
Germinal center (GC) B cells readily undergo apoptosis, a tendency which can be suppressed in vitro by immobilized anti-Ig; mAb to CD40 and soluble CD23 (in synergy with IL-1 alpha) also effect rescue of GC cells from programmed cell death. In the present study, the signals which stimulate rescued GC populations to DNA synthesis have been examined and compared to those established for the activation of follicular mantle (FM) B cells. On co-culture with anti-Ig, optimal responses in FM B cells can be achieved with a combination of IL-4 and CD40 antibody; these activities also provided a modest stimulus to GC cells but, for this population, anti-Ig was ineffective at augmenting the response further. Stimulations of GC B cells were enhanced, however, when performed on a support of primary fetal lung fibroblasts; a major influence of stroma was to promote, by direct cell-cell contact, the CD40-dependent survival of GC B cells. FM B cells were relatively independent of such stromal support. In marked contrast to FM cells, GC B cells were found to respond by enhanced DNA synthesis to IL-2 even when quite low concentrations of the factor were present (IC50 = 2 U/ml). Stimulation of GC cells via this pathway was augmented almost 2-fold on the inclusion of anti-Ig whereas neither fibroblasts, IL-4, nor CD40 antibody made any additional contribution to the IL-2-dependent response. The requirements found for stimulating GC cells in vitro are discussed with reference to the signals that this population may encounter in appropriate microenvironments in vivo: the variety of options apparently available could reflect changing priorities at different stages of a developing GC response.
生发中心（GC）B细胞易于发生凋亡，这种趋势在体外可被固定化抗Ig抑制；抗CD40单克隆抗体和可溶性CD23（与IL-1α协同作用）也能使GC细胞从程序性细胞死亡中得到挽救。在本研究中，已对刺激获救的GC群体进行DNA合成的信号进行了检测，并与已确定的激活滤泡套（FM）B细胞的信号进行了比较。与抗Ig共培养时，IL-4和CD40抗体联合使用可使FM B细胞产生最佳反应；这些活性对GC细胞也有适度刺激，但对于该群体而言，抗Ig在进一步增强反应方面无效。然而，当在原代胎儿肺成纤维细胞支持物上进行刺激时，GC B细胞的刺激作用增强；基质的主要影响是通过直接细胞间接触促进GC B细胞的CD40依赖性存活。FM B细胞相对独立于这种基质支持。与FM细胞形成鲜明对比的是，发现GC B细胞即使在存在相当低浓度的IL-2（IC50 = 2 U/ml）时也会通过增强DNA合成来做出反应。加入抗Ig后，通过该途径对GC细胞的刺激作用增强了近2倍，而成纤维细胞、IL-4或CD40抗体对IL-2依赖性反应均无额外贡献。本文参照该群体在体内适当微环境中可能遇到的信号，讨论了体外刺激GC细胞的需求：明显可用的多种选择可能反映了发育中的GC反应不同阶段变化的优先事项。
