PROLIFERATION OF CD3(-) SINGLE-POSITIVE NORMAL T-CELLS WAS SUPPRESSEDIN B-CELL-DEFICIENT LPR MICE() B220()

It is known that lpr mice develop systemic lymphadenopathy and lupus e rythematosus-like autoimmune disease that are associated with the accu mulation of CD4(-)CD8(-) (double-negative; DN) CD3(+) B220(+) abnormal T cells as well as normal mature CD4(+) or CD8(+) single-positive (SP ) CD3(+) T cells. In order to clarify the role of B cells in the lymph oproliferation and autoimmunity of lpr mice, we created B-cell-deficie nt C57BL/6 (B6) lpr mice (B6lpr/pr mu MT/mu MT) by crossing B6lpr/lpr mice with B6 mu MT/mu MT mice in which the B-cell development was arre sted at pre-B stage owing to a targeted disruption of the immunoglobul in mu heavy-chain gene locus. In the B-cell-deficient B6-lpr mice, bot h lymphadenopathy and splenomegaly were markedly suppressed. Although the accumulation of both CD3(+) B220(-) SP normal T cells and CD3(+) B 220(+) DN abnormal T cells was inhibited in the B-cell-deficient lpr m ice, the decrease in numbers of CD3(+) B220(-) SP normal T cells occur red more strikingly than that of the CD3(+) B220(+) DN abnormal T cell s. Glomerulonephritis did not develop in the B-cell-deficient lpr mice over 40 weeks. The present results indicate that the B sells thus pla y a crucial role in the extensive proliferation of normal CD3(+) B220( -) mature SP T cells rather than the accumulation of abnormal DN T cel ls.