B-CELL GENOTYPE DETERMINES THE FINE SPECIFICITY OF AUTOANTIBODY IN LPR MICE

Anti-Sm Abs are specific markers of human systemic lupus erythematosus (SLE) and of murine models of this disease. In humans, anti-Sm Abs ar e mostly IgG1, and in MRL/lpr mice, IgG2a; both are T-dependent isotyp es, Other lpr strains, such as B6/lpr, do not produce anti-Sm Ab spont aneously. The present study was aimed at identifying the cellular expr ession of background genes responsible for generation of the anti-Sm A b response in MRL/lpr mice. We used double chimeric mice made by trans ferring MRL/lpr and B6/lpr bone marrows into irradiated allotype heter ozygous F, mice, Five mo after reconstitution, FAGS analysis of lymph node (LN) and spleen cells revealed that both MRL/lpr and B6/lpr cells coexisted in roughly equal numbers. Ab produced by each donor could b e distinguished by allotype-specific assays. IgG2a anti-Sm was made on ly by MRL-derived B cells despite the presence of T cells that might p otentially provide help to the B6/lpr B cells. The frequency of anti-S m Ab-producing individuals was similar to that of unmanipulated MRL/lp r mice (about 25%). IgG2a anti-chromatin and total Igc2a was mostly do minated by the MRL-derived B cells. BG-derived B cells produced more r heumatoid factor (RF) against their own IgG2b(b), while RF against IgG 2a was dominated by MRL-derived B cells, This suggests that the contro l of the production of particular autoantibody specificities, such as anti-Sm, is determined by the expression of MRL or B6 background genes in B cells.