Dighiero G, Lim A, Poncet P, Kaushik A, Ge X R, Mazié J C
d'Immunopathologie, Institut Pasteur, Paris, France.
Immunology. 1987 Nov;62(3):341-7.
In the studies presented here, age-related natural antibody specificities have been investigated in the autoimmune NZB mouse strain by cell fusion. The monoclonal immunoglobulins (MIg) secreted by productive hybridoma clones were examined for their antibody activities against a panel of antigens, including single- and double-stranded DNA, actin, tubulin, myosin, bromelain-treated mouse red blood cells (BrMRBC) and TNP-BSA, employing both direct and competitive enzyme immunoassays. The antibody specificities against this panel of antigens were strikingly frequent among hybridoma clones from neonatal NZB (49%) mice, compared to normal BALB/c neonates (8.8%) shown earlier. Among neonatal hybridomas with known antigen reactivities, 73% of the clones exhibited polyspecific binding. In contrast, the majority of hybridomas from 5- and 7-month-old NZB spleen reacted monospecifically (76%) with the antigens tested. Such a characteristic reactivity pattern reflects an age-related evolution of B-cell repertoire expression. Unlike normal BALB/c mice, a high frequency of monospecific TNP-hapten-reactive clones (75%) was noticed among hybridomas of known antigen reactivities from 5- and 7-month-old NZB-strain mice, an age when autoimmune haemolytic anaemia sets in. In conclusion, an elevated frequency of autoreactive clones among neonates (49%) and an aberrant expression of TNP-reactive clones in adults seem to be an outward signal of certain discrepancies at the level of B-cell repertoire expression in autoimmune NZB-strain mice.
在本文所呈现的研究中，通过细胞融合对自身免疫性NZB小鼠品系中与年龄相关的天然抗体特异性进行了研究。利用直接和竞争性酶免疫测定法，检测了有生产能力的杂交瘤克隆分泌的单克隆免疫球蛋白（MIg）针对一系列抗原的抗体活性，这些抗原包括单链和双链DNA、肌动蛋白、微管蛋白、肌球蛋白、菠萝蛋白酶处理的小鼠红细胞（BrMRBC）和TNP-BSA。与先前显示的正常新生BALB/c小鼠（8.8%）相比，来自新生NZB（49%）小鼠的杂交瘤克隆中，针对这一系列抗原的抗体特异性极为常见。在具有已知抗原反应性的新生杂交瘤中，73%的克隆表现出多特异性结合。相比之下，来自5个月和7个月大的NZB脾脏的大多数杂交瘤与所检测的抗原发生单特异性反应（76%）。这种特征性的反应模式反映了B细胞库表达与年龄相关的演变。与正常BALB/c小鼠不同，在5个月和7个月大的NZB品系小鼠（此时自身免疫性溶血性贫血开始出现）中，具有已知抗原反应性的杂交瘤中，单特异性TNP-半抗原反应性克隆的频率很高（75%）。总之，新生小鼠中自身反应性克隆频率升高（49%）以及成年小鼠中TNP反应性克隆的异常表达似乎是自身免疫性NZB品系小鼠B细胞库表达水平存在某些差异的外在信号。
