McKearn J P, Miller G W, Quintáns J
Immunology. 1978 Jun;34(6):1063-9.
This study was designed to examine aberrations of immune responses in autoimmune NZB strain mice during ageing, at the level of individual B cell clones. The response to phosphorylcholine (PC) was chosen because murine responses to PC are restricted to a few B cell clones and can be characterized with idiotypic markers. Responses to both thymus-dependent (TD) and thymus-independently (TI) PC-containing antigens were measured in mice ranging from 1 to 62 weeks of age. We found that: (1) TD responses to phosphorylcholine keyhole limpet haemocyanin (PC-KLH) decreased markedly (about 17-fold) between 28 and 62 weeks of age. TI responses to the R36a strain pneumococcus decreased only slightly during the same period. (2) The PFC responses to both antigens became markedly prolonged in mice older than 24 weeks. (3) The NZB response to either antigen is essentially monoclonal, as measured by inhibition of PFC with specific anti-idiotype serum and PC hapten. No age-related alteration in avidity or idiotype expression was observed. Our results demonstrate that no aberrant PC-reactive B cell clones appear in old NZB, and lend support to the notion that the abnormalities observed are due to defective regulatory mechanisms.
本研究旨在从单个B细胞克隆水平,检测自身免疫性NZB品系小鼠衰老过程中的免疫反应异常。选择对磷酸胆碱(PC)的反应进行研究,是因为小鼠对PC的反应局限于少数B细胞克隆,并且可用独特型标记进行表征。在1至62周龄的小鼠中,测定了对胸腺依赖性(TD)和胸腺非依赖性(TI)含PC抗原的反应。我们发现:(1)对磷酸胆碱钥孔戚血蓝蛋白(PC-KLH)的TD反应在28至62周龄之间显著下降(约17倍)。同期对R36a株肺炎球菌的TI反应仅略有下降。(2)在24周龄以上的小鼠中,对两种抗原的PFC反应明显延长。(3)用特异性抗独特型血清和PC半抗原抑制PFC测定,NZB对任一抗原的反应基本上是单克隆的。未观察到亲和力或独特型表达的年龄相关变化。我们的结果表明,老年NZB中未出现异常的PC反应性B细胞克隆,并支持所观察到的异常是由于调节机制缺陷这一观点。