Reduced development of CD4 − 8 − B220 + T cells but normal autoantibody production in lpr / lpr mice lacking major histocompatibility complex class I molecules

Abstract The lpr gene has recently been shown to encode a functional mutation in the Fas receptor, a molecule involved in transducing apoptotic signals. Mice homozygous for the lpr gene develop an autoimmune syndrome accompanied by massive accumulation of double‐negative (DN) CD4 − 8 − B220 + T cell receptor‐α/β + cells. In order to investigate the origin of these DN T cells, we derived lpr / lpr mice lacking major histocompatibility complex (MHC) class I molecules by intercrossing them with β2‐microglobulin (β2m)‐deficient mice. Interestingly, these lpr β2m–/– mice develop 13‐fold fewer DN T cells in lymph nodes as compared to lpr / lpr wild‐type ( lpr WT) mice. Analysis of anti‐DNA antibodies and rheumatoid factor in serum demonstrates that lpr β2m–/– mice produce comparable levels of autoantibodies to lpr WT mice. Collectively our data indicate that MHC class I molecules control the development of DN T cells but not autoantibody production in Ipr / lpr mice and support the hypothesis that the majority of DN T cells may be derived from cells of the CD8 lineage.