B lymphocytes from the autoimmune-prone mouse strain MLR/lpr manifest an intrinsic defect in tetraparental MRL/lpr in equilibrium DBA/2 chimeras.

Data are presented showing that MRL/lpr in equilibrium DBA/2 tetraparental (allophenic) chimeras, unlike conventional lpr/lpr----+/lpr bone marrow chimeras, fail to develop graft-vs-host disease; instead they develop full-blown lymphoproliferation and autoantibody formation typical of unmanipulated MRL/lpr mice. The increase in the splenic and especially the lymph node mass is comprised predominantly of MRL/lpr-derived cells and all of the serum IgG2a is MRL/lpr derived. This dominance of MRL/lpr lymphoid activity occurred even in chimeras where greater than 90% of the skin and/or bone marrow cells were of the DBA/2 type. These results demonstrate the failure of the lpr environment to recruit normal B and T cells into the autoimmune process, the inability of normal cells to suppress MRL/lpr disease, and indicate further that the lpr mutation has an intrinsic effect on lymphocytes of both the B and T lineages.