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Molecular Signatures of Anti-nuclear Antibodies: Contributions of Specific Light Chain Residues and a Novel New Zealand Black V1 Germline Gene ¹

Simmons Arthritis Research Center and Center for Immunology, University of Texas Southwestern Medical School, Dallas, TX 75235

Although the Ig H chains of anti-nuclear Abs (ANA) have been described to possess certain shared molecular signatures, it remains unclear whether the L chains of these Abs also possess distinctive molecular features. The present study examines this by generating and analyzing two comprehensive murine Ig L chain databases, one consisting of 264 monoclonal ANAs and the other consisting of 145 non-ANAs, drawn from previously published work. Importantly, clonal replicates were represented only once each, so as to minimize bias. ANAs and non-ANAs did not differ in V family or J gene usage, nor in their mutation frequencies. Interestingly, the L chains of ANAs exhibited differential usage of certain complementarity-determining region residues, arising almost entirely from the increased usage of certain V germline genes, notably, V ai4 among anti-dsDNA ANAs, V23–45 among anti-ssDNA ANAs, and V21–12 among non-ANAs. Finally, prompted by the increased prevalence of a particular V1 family sequence among ANAs, we proceeded to clone a novel New Zealand Black V1 germline gene, named bb1.1, which appears to be frequently used to encoded anti-ssDNA Abs. Collectively, these studies underline the potential contribution of particular V germline genes in promoting or thwarting DNA binding.

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