The Journal of Immunology, Vol 152, Issue 9 4489-4499, Copyright © 1994 by American Association of Immunologists

ARTICLES

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

BA Jacobson, J Sharon, H Shan, M Shlomchik, MG Weigert and A Marshak-Rothstein
Department of Pathology, Boston University School of Medicine, MA 02118.

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 gamma 3. The RF bound specifically to the MRL gamma 2 a allotype (Igh- 1j) but not to the B6 gamma 2a allotype (Igh-1b). The germ-line antibody was also found to bind gamma 2a 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 (Kd) 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.

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