Study of self reactive antibodies in kappa-light chain deficient mice

The kappa chain deficient mouse strain represents an excellent experimental system for studying the contribution of lambda light chains to the antibody repertoire. Here, we have studied the contribution of lambda chains to the generation of self reactive antibodies including RFs in kappa deficient mice with 129/sv background. These mutant mice produce rheumatoid factors similar to 129/sv mice and these antibodies are primarily encoded by lambda 2. This may be due to the production of RF by peritoneal B lymphocytes which belong to Ly1 B subset. Peritoneal B cell selectively produce lambda 2 and lambda 3 isotypes. Though lambda 1 positive RF is not detectable in the sera, lambda 1 positive specific precursor B cells are present in these mice and they can be activated by T-independent antigens. Our studies show that these mice also spontaneously produce anti-dsDNA antibodies bearing lambda 1 light chain but do not produce self reactive antibodies specific for eight different autoantigens. However, B cell precursors expressing lambda chains specific for autoantigens like collagen II, III, IV and histone 2A are present in the B cell repertoire of kappa-deficient mice. Thus, our results demonstrate that lambda light chain can compensate, to some extent, the lack of kappa chain repertoire, not only against foreign antigens, as observed previously, but also against a number of autoantigens.