One current focus in the lab includes the maturation and differentiation of B cells with the intent to identify key transcription control proteins that regulate this process.  Mouse B cells enter the spleen from the bone marrow requiring a number of maturation steps to insure they are competent to respond to antigen following an infection.  These immature B cells must negotiate through a series of differentiation checkpoints, requiring transcriptional induction and suppression of key target genes.  We have identified a number of the target gene products required for such maturation and are now defining the control proteins that regulate their expression. One of our ultimate goals is to create strains of mice that lack these key control proteins required for these maturation steps (or over-express the gene products) to define the cellular and molecular consequences of their absence.

The longest running project in the lab has been to study the structure, expression and function of a set of mouse proteins known as the complement receptors.  These proteins are critical for controlling complement activation during immune reactions and serve to assist in the production of the full range of B cell products. Inappropriate expression of such proteins (such as engineered mouse anomalies or human deficiencies) can give rise to a range of symptoms including autoimmunity, susceptibility to natural infections and a degraded antibody response.  We have created strains of mice either deficient in such proteins (deficiency of the CD21 gene products) or with engineered germ line mutations that result in either mutant protein production or inappropriate expression.  We are currently analyzing such mice and are defining previously unknown feedback pathways that this set of proteins regulate.

A relatively new project in the lab focuses upon defining the maturation steps T cells take in positive and negative selection within the thymus. We have identified a novel transcriptional repressor that is expressed during this time frame and are currently identifying target genes that it regulates during these differentiation steps.  Identification and modulation of such genes should aid in our understanding of the development of a functional T cell repertoire and response.

Staff

• Kristin Roundy
• Amanda Jacobson
• Irina Debnath
• Timothy Dahlem