Autoimmunity and increased c-myb transcription.

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder characterized by lymphadenopathy, autoimmune phenomena, and increased risk of lymphoma.
• A specific genetic mutation, lpr, in mice is known to induce a similar syndrome.
• The role of specific genes, such as myb, in the pathogenesis of ALPS is not fully understood.

Purpose of the Study:

• To investigate the role of the myb gene in the development of autoimmune lymphoproliferative syndrome in lpr/lpr mice.
• To compare myb gene expression in affected mice with human lymphoproliferative disorders.
• To determine if increased myb expression is a general feature of lymphocyte activation.

Main Methods:

• Analysis of lymphoid organs from lpr/lpr mice and control littermates.
• Quantification of myb RNA levels in lymphoid cells.
• Comparison of myb expression patterns in mouse T cells stimulated to proliferate with mitogens.
• Examination of c-myb expression in human lymphoproliferative disorder samples.

Main Results:

• lpr/lpr mice exhibited significantly increased amounts of myb RNA in their lymphoid organs.
• Elevated c-myb expression was also observed in a comparable human lymphoproliferative disorder.
• Activated mouse T cells undergoing proliferation did not show a marked increase in myb RNA levels.

Conclusions:

• The lpr gene mutation is associated with increased myb gene expression in the context of autoimmune lymphoproliferative syndrome.
• Increased myb expression may be a contributing factor in the pathogenesis of ALPS and similar human disorders.
• Marked myb expression is not a universal characteristic of lymphocyte activation and proliferation.