The abnormal T cells attack the body's own cells and tissues, accounting for the autoimmune features of Omenn syndrome. The decrease in lymphocyte function leads to a reduction in the numbers of B cells, but the number of T cells is typically normal. The abnormal B and T cells result in the frequent, life-threatening infections of Omenn syndrome. As a result, V(D)J recombination is diminished and the diversity of proteins on the surface of B cells and T cell is severely limited, impairing the cells' ability to recognize foreign invaders and fight infections. These changes can impair RAG complex formation and function, including its ability to bind to DNA. Most of the RAG1 gene mutations that cause Omenn syndrome change single protein building blocks (amino acids) in the RAG1 protein. Without treatment, Omenn syndrome is often fatal in infancy.
Omenn syndrome is characterized by a reduced ability to fight infections and autoimmunity, in which the immune system attacks the body's own tissues and organs. This condition is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria, viruses, and fungi. The variety of proteins produced throughout life following V(D)J recombination provides greater recognition of foreign invaders and allows the body to fight infection efficiently.Īt least 70 mutations in the RAG1 gene have been found to cause an immune system disorder called Omenn syndrome. This process of DNA rearrangement within B cells and T cells is repeated multiple times in different areas so that the V, D, and J segments are arranged in various combinations. The RAG complex makes small cuts in the DNA between the segment and the RSS so the segment can be separated and moved to a different area in the gene. The RAG complex is involved in this process, which is known as V(D)J recombination.ĭuring V(D)J recombination, the RAG complex attaches (binds) to a section of DNA called a recombination signal sequence (RSS), which is next to a V, D, or J segment. During protein production within lymphocytes, these gene segments are rearranged in different combinations to increase variability of the resulting proteins. The genes from which these proteins are made contain segments known as variable (V), diversity (D), and joining (J) segments. These proteins need to be diverse to be able to recognize a wide variety of substances. These cells have special proteins on their surface that recognize foreign invaders and help protect the body from infection. This complex is active in immune system cells (lymphocytes) called B cells and T cells. The RAG1 gene provides instructions for making a member of a group of proteins called the RAG complex.
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