Part III—Proteins Required for B and T Cell Development Baby Joe’s doctors diagn

Part III—Proteins Required for B and T Cell Development
Baby Joe’s doctors diagnosed his condition as severe combined immunodeficiency (SCID). This disease is life-threatening; without treatment, it is usually fatal in childhood. SCID can be caused by several genetic mutations. Many of these mutations are in genes involved in the normal development of B and T cells.
B cells begin to express immunoglobulin (Ig) proteins early in their development. If a developing B cell does not express an Ig, it dies. Similarly, developing T cells die if they do not express the required T cell receptor (TCR).
In order for B cells to express Ig proteins and for T cells to express TCR proteins, molecular rearrangements of the DNA encoding these proteins must take place. Before this rearrangement occurs, the genes are not functional; they have early stop codons and do not encode a fully functional protein product. However, in
each normally developing B or T cell, the DNA composing the Ig or TCR gene is physically cut and spliced to yield functional genes that encode the full, functional protein. This process is referred to as somatic recombination.
Somatic recombination requires the action of many different enzymes. Some of these enzymes are expressed in all types of cells and are involved in DNA repair. However, some of the enzymes involved are only expressed in B and T cells. One such enzyme is called RAG, or Recombination-Activating Gene. The role of RAG in B cell development is summarized below; it plays a similar role in T cell development.
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A sample of Baby Joe’s DNA was sent for sequence analysis, which revealed mutations in both copies of his RAG genes. The mutations in both genes were frameshift mutations, resulting in a complete lack of expression of functional RAG protein.
Questions
1. Explain how a lack of rag protein results in the phenotype observed in Baby Joe.
2. Why doesn’t the mutation in RAG affect cell types other than B cells and T cells?