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Somatic Hypermutation in Autoimmunity



Project Description

A hallmark of systemic autoimmune disease is the presence of serum autoantibodies directed against conserved nuclear antigens such as DNA.  Our recent work has demonstrated that B cells producing these anti-nuclear antibodies (ANA) can be generated from nonautoreactive B cells by the process of somatic hypermutation (SHM), which normally diversifies antibody variable (V) region genes expressed by B cells during immune reactions against pathogens. The potential of SHM to turn a normal B cell into one that is autoreactive has important implications regarding the genesis of autoimmune disease.  Is this a frequent occurrence?  The project I envision will address this basic question.
AGC and AGT serine codons within antibody V region genes are particularly vulnerable targets of SHM with regards to autoreactivity, because they are easily converted to Arg codons by SHM.  And Arg residues contribute substantially to binding interactions between the antibody V region and nuclear antigens.  Therefore, the project will involve extracting germline V region gene sequences from public databases and analyzing them for serine codon use. Such an analysis will provide an important insight into the origin of ANA.  If AGC and AGT codons are abundant in CDRs, it is likely that somatic mutations frequently generate ANA from normal B cells participating in immune responses to foreign material.

Mentor Name

Wysocki, Lawrence J.

Mentor Location

National Jewish Health Goodman Bldg. K902

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Funding Department/Program


Area of Study

Immunology and Autoimmune Diseases




Cell Biology, Molecular Biology, and Genetics

Disease or Symptom

Basic Human Processes

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Created at 6/17/2011 8:45 AM by Vetter, Stephanie
Last modified at 7/9/2013 1:47 PM by Watts, Katie