TY - JOUR
T1 - Molecular signatures of anti-nuclear antibodies
T2 - Contributions of specific light chain residues and a novel New Zealand Black Vκ1 germline gene
AU - Liang, Zhiyan
AU - Chen, Cui
AU - Mohan, Chandra
PY - 2003/10/1
Y1 - 2003/10/1
N2 - 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 Vκ family or Jκ 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 Vκ germline genes, notably, Vκ ai4 among anti-dsDNA ANAs, Vκ23-45 among anti-ssDNA ANAs, and Vκ21-12 among non-ANAs. Finally, prompted by the increased prevalence of a particular Vκ1 family sequence among ANAs, we proceeded to clone a novel New Zealand Black Vκ1 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 Vκ germline genes in promoting or thwarting DNA binding.
AB - 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 Vκ family or Jκ 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 Vκ germline genes, notably, Vκ ai4 among anti-dsDNA ANAs, Vκ23-45 among anti-ssDNA ANAs, and Vκ21-12 among non-ANAs. Finally, prompted by the increased prevalence of a particular Vκ1 family sequence among ANAs, we proceeded to clone a novel New Zealand Black Vκ1 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 Vκ germline genes in promoting or thwarting DNA binding.
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U2 - 10.4049/jimmunol.171.7.3886
DO - 10.4049/jimmunol.171.7.3886
M3 - Article
C2 - 14500691
AN - SCOPUS:0141955060
SN - 0022-1767
VL - 171
SP - 3886
EP - 3894
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -