Restricted CDR3 length of the heavy chain is characteristic of six randomly isolated disease-associated VH J558+ IgM autoantibodies in lupus prone motheaten mice

International Immunology
V LipsanenA Kaushik

Abstract

To investigate the origin of disease-associated IgM autoantibodies (AAb), we compared the genetic and structural characteristics of IgM AAb from autoimmune prone motheaten (mev) mice with natural autoantibodies (NAAb) from normal background C57/BL6 strain. Six hybridoma-derived IgM molecules each were obtained both from mev mice, at the terminal stage of systemic autoimmune disease, and from mitogen-stimulated C57/BL6 mice. These were randomly selected for VH J558 gene expression (aberrantly expressed in mev mice). The variable regions of the IgM molecules, both from autoimmune and normal mice, were encoded by unmutated germline VH genes. Disease-associated AAb from mev mice were predominantly encoded by the J558 subfamily 186.2, whereas five J558 subfamilies were utilized in NAAb originating from normal mice. Junctional diversity as a result of N or P nucleotide insertions and D-D fusions was noted among IgMs originating from both mev (mostly B-1 lymphocytes) and C57BL/6 (mostly B-2 lymphocytes) mice. Interestingly, all six J558+ IgMs from mev mice showed a restricted CDR3 length of 10 amino acids, with similar hydrophobicity indices. Four unique V-D-J rearrangements were observed among these IgMs. None of the IgMs were polyre...Continue Reading

Citations

Jul 10, 2003·Journal of Molecular Biology·Jun YinPeter G Schultz
Oct 4, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yingjia ChenWanli Liu
Sep 19, 2015·Journal of Leukocyte Biology·Jill M KramerThomas L Rothstein
Jun 9, 2005·European Journal of Immunology·Peter M Dammers, Frans G M Kroese
Nov 22, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·P M DammersF G Kroese

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