Molecular basis of immunoglobulin variable region gene usage in systemic autoimmunity

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Abstract
This review focuses on the immunoglobulin variable region (IgV) chain gene usage in patients with systemic autoimmune diseases, with particular emphasis on systemic lupus erythematosus (SLE), a condition known to be associated with the production of a number of characteristic autoantibodies as an abnormality. The IgV repertoire is shaped by a variety of molecular and selective influences that are difficult to distinguish. Studies of IgV gene rearrangement by PCR of individual B cells permitted insight in the differential impact of these processes, including somatic hypermutation and indications of receptor editing/revision. Although the majority of current data indicate that there is no major molecular abnormality in V(D)J recombination in SLE patients, abnormalities in subsequent events, such as the degree of receptor editing and somatic hypermutation, and positive and negative selection fundamentally alter the composition of the peripheral B-cell repertoire. Identification of the mechanisms that influence the IgV gene and B-cell repertoire may allow new therapeutic approaches in autoimmunity.

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