Vn. Kakkanaiah et al., B-CELL GENOTYPE DETERMINES THE FINE SPECIFICITY OF AUTOANTIBODY IN LPR MICE, The Journal of immunology, 159(2), 1997, pp. 1027-1035
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.