Experimental lupus nephritis in severe combined immunodeficient (SCID) mice: remodelling of the glomerular lesions by bystander IgM antibodies

MRL/Mp-lpr/lpr (MRL/lpr) mice develop glomerular lesions with regular varia tions in their histopathological manifestations, similar to those in lupus nephritis. These lesions are mainly either cell-proliferative or wire loop- like and are associated with glomerular deposits of immunoglobulins, most f requently IgG and IgM. We previously established a nephritogenic IgG3-produ cing hybridoma clone, B1, from an MRL/lpr mouse, which induces only a 'wire loop-like' type of glomerular lesion when injected into SCID mice. Injecti on of SCID mice with an anti-trinitrophenyl IgM antibody-producing hybridom a clone, Sp6, following injection of the B1 clone, however, resulted in the development of a 'cell-proliferative' type of glomerular lesion, associate d with an accumulation of both antibodies in glomeruli. This accumulation o ccurred even though Sp6 IgM antibodies did not react with B1 IgG3 antibodie s and vice versa. A mutant clone of Sp6, T/13 mu E/3.1, which produces anti bodies deficient in C1q binding, produced a similar effect as that of the S p6 clone, i.e. 'cell-proliferative' lesions. Again the B1 antibodies did no t react with T/13 mu E/3.1-IgM antibodies and vice versa. We therefore conc lude that bystander IgM antibodies contribute to the remodelling of glomeru lar lesions in situ, following glomerular injury by the nephritogenic antib odies.