Cyclins and Autoimmunity: Cyclin B1 Gene Expression and Restriction Fragment Length Polymorphism in Lupus-Prone Mice

Abstract

Cyclin B1 is the major component of M-phase promoting factor that plays a major role in the G2/M transition of cell cycle. We examined the expression of cyclin B1 at the protein and mRNA levels in the thymus of 12-week-old autoimmune and normal mice. We found an abundance of cyclin B1 protein (58 kDa) in the thymus of lupus-prone MRL-lpr/lpr mice, whereas the level of this protein was negligible in other strains. The level of the predominant cyclin B1 mRNA (1.7 kb) species was not markedly different in these strains, suggesting post transcriptional modification of cyclin B1 in the thymus of MRL-lpr/lpr mice. Southern blot analysis of cyclin B1 gene showed multiple forms of cyclin B1-related sequences in various murine genomes. Flow cytometry showed a significantly higher level of cells in the G2/M phase and a significantly lower level in the S phase in thymocytes of MRL-lpr/lpr compared to that in normal BALB/c mice, indicating an alteration of cell cycle machinery in thymocytes of MRL-lpr/lpr mice. Taken together, these data show that an upregulation of cyclin B1 protein and accumulation of thymocytes at the G2/M phase in MRL-lpr/lpr mice might play an important role in the aberrant development of T cells in these mice.

Key Words:

• Cyclin B1
• cell cycle
• thymus
• murine lupus
• autoimmunity
• lpr mice