EARLY INDUCTION OF ANTI-DOUBLE-STRANDED DNA ANTIBODIES IN LUPUS-PRONE MRL MICE INOCULATED WITH LY-24+ CELLS CLONED FROM LYMPH-NODE CELLS OF AN MRL/MP-LPR/LPR MOUSE - POSSIBLE EFFECT OF PUTATIVE CYTOKINES PRODUCED BY CLONED LY-24+ CELLS

We have reported that a cell line, KML1, obtained from lymph node cells of a 16-week-old female MRL/Mp-lpr/lpr (MRL/1) mouse produces a soluble factor(s) that promotes formation of anti-single-stranded (ss) DNA antibodies by cultures of spleen cells from old MRL/1 mice (>16 weeks old). Detailed examintion revealed that KML1-7 cells cloned from the cell line KML1 were only positive for the Ly-24 (Pgp-1) phenotype, and were negative for other typical phenotypes tested, such as Thy-1, Ly-1, Ly-2, Ly-4 (L3T4) and Ly-5 (B220). This finding suggested that this line was of prothymocyte or myeloid cell lineage. From day 70 after subcutaneous inoculation of KML1-7 cells into 10-week-old MRL/Mp-+/+(MRL/n) mice, IgG anti-dsDNA antibodies began to replace IgM anti-dsDNA antibodies in the serum of these mice, but anticardiolipin, anti-trinitrophenyl hapten (TNP) and anti-poly(ADP-ribose) antibodies did not increase significantly. The predominant subclasses of anti-dsDNA antibodies that increased were IgG2a and IgG2b. IgG anti-dsDNA antibodies also became detectable as early as day 22 after inoculation of KML1-7 cells into MRL/1 mice of 10 weeks old. The finding that in MRL/n mice the IgM isotype was increased first and was soon replaced by the IgG isotype was consistent with findings when spleen cells from MRL/n mice of 20 weeks old primed with ssDNA were cultured in the presence of conditioned medium containing a putative cytokine(s) (PC) produced by KML1-7 cells. These findings suggest that the PC that induces the early appearance of IgG anti-dsDNA antibodies in MRL mice is the same as that which induces production of anti-DNA antibodies in cultures of spleen cells of old MRL/1 mice (>16 weeks old) and of MRL/n mice primed with ssDNA. It is unknown whether this PC is identical to one of the interleukins reported, other than IL-2 and IL-3. © 1990.