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. 1989 Nov;84(5):1675–1678. doi: 10.1172/JCI114347

A natural autoantibody is encoded by germline heavy and lambda light chain variable region genes without somatic mutation.

K A Siminovitch 1, V Misener 1, P C Kwong 1, Q L Song 1, P P Chen 1
PMCID: PMC304036  PMID: 2509520

Abstract

While nonmutated germline variable region (V) genes have been found to encode heavy or light chains of various human autoantibodies, the use of germline V genes by both chains of a given autoantibody has not been documented. Recently, we reported that the heavy chain V gene (designated Humha346) of the Kim4.6 anti-DNA antibody is identical to a germline VH gene, 1.9III. To investigate whether this autoantibody was entirely germline encoded, we searched for the germline counterpart to the Kim4.6 V lambda segment (designated Humla146) and isolated a V lambda I gene designated Humlv117, which was identical to Humla146. Together with the sequence identity of the Kim4.6/Humha346 and 1.9III VH genes, the current data provide the first direct proof that an autoantibody can be encoded entirely by germline V genes without any somatic change. In addition, Humlv117 is the first V lambda I germline gene that has been isolated, and is highly homologous to the V lambda genes expressed in two lymphomas. Thus, this V lambda I gene should provide a useful tool for investigating the expression of the human V lambda gene repertoire, particularly with regard to autoimmune and/or lymphoproliferative diseases.

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Selected References

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