Selective expression of class II E alpha d gene in transgenic mice

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• MHC Class II genes are essential for CD4+ T cell activation and T cell help to B lymphocytes.
• Expression of MHC Class II genes is restricted and tightly regulated.
• Antigen-presenting cells (APCs) require MHC Class II expression for immune responses.

Purpose of the Study:

• To map regulatory 5' flanking regions of the MHC class II E alpha d gene.
• To understand the cell-type-specific control of E alpha d gene expression.
• To investigate the mechanisms underlying MHC Class II gene regulation in immune cells.

Main Methods:

• Utilized deletion constructs of the E alpha d gene in transgenic mice.
• Analyzed gene expression patterns within macrophage and B cell lineages.
• Investigated regulatory elements controlling E alpha d gene transcription.

Main Results:

• Identified distinct 5' flanking regions controlling E alpha d gene expression in specific cell types.
• Demonstrated dissociated expression of E alpha d within macrophage and B cell lineages.
• Presented evidence for a repressive element acting on B cells and macrophages.
• Generated transgenic mice with constitutive and inducible E alpha mRNA and I-E protein expression.

Conclusions:

• Specific regulatory elements in the 5' flanking region dictate E alpha d gene expression in a cell-type-specific manner.
• A repressive element influences E alpha d expression in both B cells and macrophages.
• Novel transgenic models allow for the study of inducible MHC Class II expression.