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

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Germline variable (V) genes encode autoantibody chains, but dual germline V gene usage for both chains of a single autoantibody was undocumented.
• Previous work identified the heavy chain V gene of the Kim4.6 anti-DNA antibody as a germline VH gene (1.9III).

Purpose of the Study:

• To determine if the Kim4.6 autoantibody was entirely encoded by germline genes.
• To identify the germline counterpart of the Kim4.6 V lambda segment (Humla146).
• To investigate the potential role of the identified V lambda I germline gene in autoimmune and lymphoproliferative diseases.

Main Methods:

• Sequence analysis of autoantibody V genes.
• Isolation and characterization of germline V lambda I genes.
• Homology searches against expressed V lambda genes in lymphomas.

Main Results:

• The germline counterpart to the Kim4.6 V lambda segment (Humla146) was identified as a V lambda I gene, Humlv117.
• Humlv117 is identical to Humla146, confirming the Kim4.6 autoantibody is entirely germline encoded without somatic mutation.
• Humlv117 is the first isolated V lambda I germline gene and shows high homology to V lambda genes in lymphomas.

Conclusions:

• This study presents the first direct proof of an autoantibody encoded entirely by germline V genes.
• The isolated V lambda I germline gene (Humlv117) is a valuable tool for studying the human V lambda gene repertoire.
• Humlv117 may be relevant for understanding autoimmune and lymphoproliferative diseases.