Role of class II molecule and T cell receptor in autoantibody production.

与NZB品系相比，NZB×NZW F1(B/W F1)杂交小鼠表现出更早的发病和更高的肾脏疾病发生率，并伴随着血清抗DNA抗体水平的显著升高。抗DNA抗体的增加主要是由于Ig G类抗体的增加。B/W F1小鼠的这些事件可以归因于来自NZB株和非自身免疫性NZW株的基因的贡献。我们用H-2同源新西兰小鼠进行的研究表明，B/W F1小鼠产生抗DNA抗体既需要NZB小鼠的H-2^d，也需要NZW小鼠的H-2^z。我们的数据还表明，与NZW的T细胞受体β链基因复合体连锁的基因在这一事件中发挥了重要作用。体外研究表明，B/WF1小鼠产生的抗DNA抗体严格依赖于产生抗体的B细胞和辅助性T细胞的相互作用。结合这些遗传学和细胞学研究，我们强烈认为NZB和NZW来源的杂合Ia分子与NZW来源的T细胞受体之间的相互作用可能是B/W F1小鼠产生抗DNA抗体所必需的。我们已经建立的H-2杂合新西兰小鼠的研究证实了H-2杂合性对产生抗DNA抗体的要求。我们现在正试图建立T细胞受体β链同源基因新西兰小鼠，并确认T细胞受体在体内和体外系统中对产生抗DNA抗体的重要作用。

As compared with the NZB strain, NZB x NZW F1 (B/W F1) hybrid mice show a much earlier onset and a higher incidence of renal disease, associated with markedly increased serum levels of anti-DNA antibodies. The increment of anti-DNA antibodies is mainly due to the increase in IgG class antibodies. These events in the B/W F1 mice can be attributed to the contribution of genes derived from both NZB and nonautoimmune NZW strains. Our studies using H-2 congenic New Zealand mice suggested that both H-2^d from NZB mice and H-2^z from NZW mice were required for IgG anti-DNA antibody production in B/W F1 mice. Our data also suggested that the gene linked to the T cell receptor beta chain gene complex of NZW has an important role in this event. The in vitro studies revealed that IgG anti-DNA antibody production in B/W F1 mice is strictly dependent on the interaction of antibody producing B cells and CD4^+ helper T cells. Together with these genetical and cellular studies, it is strongly suggested that the interplay between the hybrid Ia molecules derived from both NZB and NZW on B cells and T cell receptor from NZW may be essential for the production of IgG anti-DNA antibodies in B/W F1 mice.The requirement of H-2 heterozygosity for IgG anti-DNA antibody production was confirmed by the studies using H-2 congenic New Zealand mice, which we have already established. We are now trying to establish T cell receptor beta chain congenic New Zealand mice and to confirm the important role of T cell receptor for IgG anti-DNA antibody production in both in vivo and in vitro systems.