A correlation between IgG class antibody production and glomerulonephritis in the murine chronic graft-versus-host reaction.

A graft-versus-host reaction (GVHR) was induced in (B10 x DBA/2)F1 (BDF1) and (BALB/c x A)F1 (CAF1) murine recipients by injection of their parental or B10.D2-derived spleen cells. The incidences of glomerulonephritis and autoantibody production were then correlated. All of the BDF1 mice that received DBA/2 spleen cells (termed DBA/2----BDF1) and 33% of the CAF1 mice that received BALB/c spleen cells (BALB/c----CAF1) developed glomerulonephritis. However, in other combinations (B10.D2----BDF1, A/J----CAF1) no significant glomerular lesions were observed. An analysis of antibodies by ELISA revealed that the groups with renal disease showed a significant polyclonal elevation of IgG class antibodies, including autoantibodies (anti-DNA, anti-MRBC, and NTA) and a conventional antibody (anti-TNP-KLH). No significant IgG class antibody production was observed in the groups that did not develop glomerulonephritis. Thus, it was suggested that an IgM to IgG class switch is important in the development of glomerulonephritis in GVHR. Other factors also appear to be involved. Only 33% of BALB/c----CAF1 developed glomerulonephritis, even though a level of IgG class antibody production was comparable to that observed in DBA/2----BDF1 in which 100% showed severe glomerulonephritis.