Variable Region Sequence Analysis of Anti-DNA Antibodies: Evidence for a Family of Closely Related Germ-Line VH Genes Encoding Lupus Autoantibodies

Mary H. Foster, Michael P. Madaio, Kathleen J. Barrett

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cloning and sequencing of the V regions of the anti-DNA monoclonal antibodies (mAbs), H438 and H130, indicate that H438 is encoded by a J558 VH gene, a single D region nucleotide, and unmutated JH1, Vx-1C and Jx1 genes, and the H130 L chain is encoded by a Vx-21 subgroup gene and Jx1 gene. Identification of VH438, which shared VH hybridization pattern with 6% of a panel of 352 MRL/lpr hybridomas, suggests that the frequency of J558 use among spontaneously activated B cells in MRL/1pr mice is greater than previously reported. The VHH438 J558 family gene is identical to VHPAR, which encodes the independently derived MRL/lpr autoantibody, MRP-2, and is highly homologous to the previously reported VHH130, which is identical to a BALB/c germ-line VH gene. Comparison of consensus sequences of homologous autoantibodies and previously reported restriction mapping suggest that a minimum of three highly related J558 germ-line genes encode lupus autoantibodies.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalDNA and cell biology
Volume11
Issue number3
DOIs
StatePublished - Apr 1992

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Antinuclear Antibodies
Germ Cells
Autoantibodies
Sequence Analysis
Genes
Restriction Mapping
Consensus Sequence
Hybridomas
Organism Cloning
B-Lymphocytes
Nucleotides
Monoclonal Antibodies

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Variable Region Sequence Analysis of Anti-DNA Antibodies : Evidence for a Family of Closely Related Germ-Line VH Genes Encoding Lupus Autoantibodies. / Foster, Mary H.; Madaio, Michael P.; Barrett, Kathleen J.

In: DNA and cell biology, Vol. 11, No. 3, 04.1992, p. 175-182.

Research output: Contribution to journalArticle

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abstract = "Cloning and sequencing of the V regions of the anti-DNA monoclonal antibodies (mAbs), H438 and H130, indicate that H438 is encoded by a J558 VH gene, a single D region nucleotide, and unmutated JH1, Vx-1C and Jx1 genes, and the H130 L chain is encoded by a Vx-21 subgroup gene and Jx1 gene. Identification of VH438, which shared VH hybridization pattern with 6{\%} of a panel of 352 MRL/lpr hybridomas, suggests that the frequency of J558 use among spontaneously activated B cells in MRL/1pr mice is greater than previously reported. The VHH438 J558 family gene is identical to VHPAR, which encodes the independently derived MRL/lpr autoantibody, MRP-2, and is highly homologous to the previously reported VHH130, which is identical to a BALB/c germ-line VH gene. Comparison of consensus sequences of homologous autoantibodies and previously reported restriction mapping suggest that a minimum of three highly related J558 germ-line genes encode lupus autoantibodies.",
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N2 - Cloning and sequencing of the V regions of the anti-DNA monoclonal antibodies (mAbs), H438 and H130, indicate that H438 is encoded by a J558 VH gene, a single D region nucleotide, and unmutated JH1, Vx-1C and Jx1 genes, and the H130 L chain is encoded by a Vx-21 subgroup gene and Jx1 gene. Identification of VH438, which shared VH hybridization pattern with 6% of a panel of 352 MRL/lpr hybridomas, suggests that the frequency of J558 use among spontaneously activated B cells in MRL/1pr mice is greater than previously reported. The VHH438 J558 family gene is identical to VHPAR, which encodes the independently derived MRL/lpr autoantibody, MRP-2, and is highly homologous to the previously reported VHH130, which is identical to a BALB/c germ-line VH gene. Comparison of consensus sequences of homologous autoantibodies and previously reported restriction mapping suggest that a minimum of three highly related J558 germ-line genes encode lupus autoantibodies.

AB - Cloning and sequencing of the V regions of the anti-DNA monoclonal antibodies (mAbs), H438 and H130, indicate that H438 is encoded by a J558 VH gene, a single D region nucleotide, and unmutated JH1, Vx-1C and Jx1 genes, and the H130 L chain is encoded by a Vx-21 subgroup gene and Jx1 gene. Identification of VH438, which shared VH hybridization pattern with 6% of a panel of 352 MRL/lpr hybridomas, suggests that the frequency of J558 use among spontaneously activated B cells in MRL/1pr mice is greater than previously reported. The VHH438 J558 family gene is identical to VHPAR, which encodes the independently derived MRL/lpr autoantibody, MRP-2, and is highly homologous to the previously reported VHH130, which is identical to a BALB/c germ-line VH gene. Comparison of consensus sequences of homologous autoantibodies and previously reported restriction mapping suggest that a minimum of three highly related J558 germ-line genes encode lupus autoantibodies.

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