Santulli-Marotto S, Retter M W, Gee R, Mamula M J, Clarke S H
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599, USA.
Immunity. 1998 Feb;8(2):209-19. doi: 10.1016/s1074-7613(00)80473-2.
Anti-Sm and anti-ssDNA transgenic (Tg) mice were generated using the VH-D-JH rearrangement of an anti-Sm hybridoma of MRL/Mp-lpr/lpr origin. B cells of each specificity account for 15%-35% of the splenic repertoire, but no circulating anti-Sm or anti-ssDNA antibodies are detected. Most autoreactive cells exhibit an immature B cell phenotype and have short half-lives equivalent to those of non-Tg immature B cells. However, at least some anti-Sm B cells are functional, because immunization with murine snRNPs induces anti-Sm secretion. We propose that anti-Sm and anti-ssDNA are eliminated during the transition to mature B cells and that this late stage of tolerance induction is consequential to their spontaneous activation in murine lupus.
利用源自MRL/Mp-lpr/lpr的抗Sm杂交瘤的VH-D-JH重排，制备了抗Sm和抗单链DNA转基因（Tg）小鼠。每种特异性的B细胞占脾脏细胞库的15%-35%，但未检测到循环抗Sm或抗单链DNA抗体。大多数自身反应性细胞表现出未成熟B细胞表型，半衰期与非转基因未成熟B细胞相当。然而，至少一些抗Sm B细胞具有功能，因为用鼠源小核核糖核蛋白免疫可诱导抗Sm分泌。我们提出，抗Sm和抗单链DNA在向成熟B细胞转变过程中被清除，并且这种晚期耐受诱导与它们在小鼠狼疮中的自发激活有关。
