An isotype switched and somatically mutated rheumatoid factor clone isolated from a MRL-lpr/lpr mouse exhibits limited intraclonal affinity maturation

Bruce A. Jacobson, Jacqueline Sharon, Hua Shan, Mark Shlomchik, Martin G. Weigert, Ann Marshak-Rothstein

Research output: Contribution to journalArticle

Abstract

Employing site-directed mutagenesis we have reconstructed and expressed the germ-line precursor of an expanded rheumatoid factor (RF) clone. This RF clone, designated clone F, was isolated from an autoimmune MRL/MpJ-lpr/lpr mouse. Most of the clone members were extensively mutated and isotyped- switched. The predominant isotype of clone F was γ3. The RF bound specifically to the MRL γ2a allotype (lgh-1(j)) but not to the B6 γ2a allotype (Igh-1b). The germ-line antibody was also found to bind γ2a in an RF assay. The affinities of the germ-line RF and representative members of the clone were measured in an ELISA-based equilibrium binding assay. The dissociation constant (K(d)) of the germ-line RF was 2.5 x 10-6 M. All of the expressed clone members had affinities within a two- to sixfold range of the germ line, indicating that the mechanisms of somatic hypermutation and selection resulted in only limited affinity maturation of this autoantibody clone.

Original languageEnglish (US)
Pages (from-to)4489-4499
Number of pages11
JournalJournal of Immunology
Volume152
Issue number9
StatePublished - May 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'An isotype switched and somatically mutated rheumatoid factor clone isolated from a MRL-lpr/lpr mouse exhibits limited intraclonal affinity maturation'. Together they form a unique fingerprint.

  • Cite this

    Jacobson, B. A., Sharon, J., Shan, H., Shlomchik, M., Weigert, M. G., & Marshak-Rothstein, A. (1994). An isotype switched and somatically mutated rheumatoid factor clone isolated from a MRL-lpr/lpr mouse exhibits limited intraclonal affinity maturation. Journal of Immunology, 152(9), 4489-4499.