Resting B cells from New Zealand Black mice demonstrate a defect in apoptosis induction following surface IgM ligation.

Abstract

New Zealand Black (NZB) mice spontaneously develop autoimmune disease, usually characterized by an autoimmune hemolytic anemia, and NZB genes are essential for a severe systemic lupus-like disease in (NZB x NZW)F1 mice. We have found that resting B cells from NZB mice demonstrate a pronounced defect, compared with five normal strains, in apoptosis induction after cross-linking with anti-IgM Abs. In contrast, spontaneous apoptosis of NZB B cells in culture was similar to normal strains. B cells from young (NZB x SM/J)F1 and (NZB x NZW)F1 mice underwent apoptosis normally, indicating that the NZB defect in apoptosis is a recessive trait. However, older (8-32 wk) predisease (NZB x NZW)F1 mice manifested a similar defect in apoptosis induction. The analysis of NXSM recombinant inbred mice derived from NZB and SM/J, in addition to backcross mice, suggested that the NZB apoptosis defect is a multigenic trait. Interestingly, resting B cells form B6.lpr and B6gld mice underwent apoptosis following anti-IgM treatment at a level similar to that of the C57BL/6 parental strain. Thus, the induced apoptosis of resting B cells and the NZB defect are likely not related to either Fas or Fas ligand. We propose that this phenotypic defect in apoptosis induction, or the biochemical alteration that underlies the defect, may be casually related to autoimmune disease in NZB mice and its contribution to lupus-like disease in (NZB x NZW)F1 mice.