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Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes

✍ Scribed by Reinhard Kofler; Daniel J. Noonan; Robert Strohal; Robert S. Balderas; Niels P. H. Moller; Frank J. Dixon; Argyrios N. Theofilopoulos


Publisher
John Wiley and Sons
Year
1987
Tongue
English
Weight
547 KB
Volume
17
Category
Article
ISSN
0014-2980

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✦ Synopsis


Molecular analysis of the murine lupus-associated anti-self response: involvement of a large number of heavy and light chain variable region genes*

The mRNA encoding heavy and light chains of a hybridoma-derived monoclonal IgM,x anti-immunoglobulin (rheumatoid factor) and an IgG3,x anti-histone autoantibody from systemic lupus erythematosus and arthritis-prone MRLIMp-lpr/lpr mice have been molecularily cloned, and the nucleotide sequences corresponding to their variable regions have been determined. To investigate whether autoantibodies with specificities frequently observed in lupus disease might share common structural components, the sequences obtained in this study have been compared with those of a monoclonal MRLIMp-lprllpr IgM,x anti-DNA autoantibody previously analyzed in our laboratory (1. Exp. Med. 1985. 161: 805). The 3 immunoglobulins employed different heavy chain variable region (VH) genes belonging to the large 5558 VH gene family, x light chain variable region (V,) genes from 3 different V, groups, and different diversity and joining segments. Our findings suggest that murine lupusassociated autoantibodies of different specificities do not have genetic components in common to signal their self-reactive nature and are encoded by a large number of immunoglobulin gene elements.