S. Santullimarotto et al., AUTOREACTIVE B-CELL REGULATION - PERIPHERAL INDUCTION OF DEVELOPMENTAL ARREST BY LUPUS-ASSOCIATED AUTOANTIGENS, Immunity, 8(2), 1998, pp. 209-219
Anti-Sm and anti-ssDNA transgenic (Tg) mice were generated using the V
-H-D-J(H) rearrangement of an anti-Sm hybridoma of MRL/Mp-lpr/lpr orig
in. B cells of each specificity account for 15%-35% of the splenic rep
ertoire, but no circulating anti-Sm or anti-ssDNA antibodies are detec
ted. 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 immuniz
ation with murine snRNPs induces anti-Sm secretion. We propose that an
ti-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.