Reim J W, Symer D E, Watson D C, Dintzis R Z, Dintzis H M
Department of Biophysics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Mol Immunol. 1996 Dec;33(17-18):1377-88. doi: 10.1016/s0161-5890(96)00086-7.
An ongoing, T-cell dependent, secondary antibody response to an epitope can be suppressed in vivo by low molecular weight, soluble polymers, bearing multiple copies of the same epitope. This study illustrates that such suppressive T-cell independent antigen arrays target the epitope-specific, high affinity, memory B cells for long-term functional elimination. Splenocytes from hyperimmune unsuppressed donors, when adoptively transferred into irradiated recipients will readily reconstitute a secondary anti-hapten response after antigenic challenge. No such response was observed with splenocytes transferred from hyperimmune donors suppressed with antigen arrays. The extent of suppression depended on antigen array dose and duration of exposure in the donor animals. The suppressive antigen array carryover from the donors into the recipients was negligible and insufficient to account for the observed suppression. B cells from hyperimmune mice producing high affinity anti-fluorescein antibodies, generated by multiple fluoresceinated ovalbumin (FL-OVA) injections, were helped efficiently by T cells from hyperimmune donors, which were either unsuppressed or suppressed with antigen arrays. Accordingly, help from T cells, specific for the carrier protein remains intact after such suppression. Neither lipopolysaccharide (LPS), nor additional transferred carrier-primed T cells could reverse the unresponsiveness of adoptively transferred splenocytes from suppressed animals. Flow cytometry showed that the number of hapten-specific B cells was markedly reduced after suppression. Collectively, these data show that the long term elimination of an ongoing T-cell dependent antibody response by suppressive exogenous antigen arrays is due to the functional deletion of high affinity, antigen-specific B cells, even in the presence of adequate T-cell help. The long-term nature of such functional deletion strongly suggests physical deletion of the antigen-specific B cell population.
对表位的持续的、T细胞依赖性二次抗体应答在体内可被携带相同表位多个拷贝的低分子量可溶性聚合物所抑制。本研究表明，这种抑制性的非T细胞依赖性抗原阵列靶向表位特异性、高亲和力的记忆B细胞以进行长期功能性清除。来自超免疫未受抑制供体的脾细胞，当通过过继转移至受辐照受体后，在抗原刺激后将 readily 重建二次抗半抗原应答。而从用抗原阵列抑制的超免疫供体转移的脾细胞则未观察到这种应答。抑制程度取决于抗原阵列剂量以及在供体动物中的暴露持续时间。从供体进入受体的抑制性抗原阵列残留量可忽略不计，不足以解释所观察到的抑制现象。通过多次注射荧光素化卵清蛋白（FL-OVA）产生高亲和力抗荧光素抗体的超免疫小鼠的B细胞，得到了来自超免疫供体的T细胞的有效辅助，这些供体要么未受抑制，要么用抗原阵列进行了抑制。因此，在这种抑制后，针对载体蛋白的T细胞辅助作用仍然完整。脂多糖（LPS）或额外转移的经载体致敏的T细胞均不能逆转来自受抑制动物的过继转移脾细胞的无反应性。流式细胞术显示，抑制后半抗原特异性B细胞数量明显减少。总体而言，这些数据表明，抑制性外源性抗原阵列对持续的T细胞依赖性抗体应答的长期清除是由于高亲和力、抗原特异性B细胞的功能性缺失，即使在有足够T细胞辅助的情况下也是如此。这种功能性缺失具有长期性，强烈提示抗原特异性B细胞群体发生了物理性缺失。
