Failure of affinity maturation leads to increased susceptibility to immune complex glomerulonephritis

Mice, previously selected for the production of low affinity antibody after four injections of protein antigens in saline, fell into two groups on the basis of their antibody response after injection of adjuvantized antigen. One group produced antibody of sequentially rising affinity but the other produced only low affinity antibody. Mice from the latter group were interbred to produce low affinity non-maturing mice (low N/M mice). Daily injections in these mice produced a more rapid and severe glomerulonephritis than that observed in mice of the original low affinity line. Male low N/M mice were more severely affected than female low N/M mice. Susceptibility to the disease were associated not only with an inability to produce the maturational transition from low affinity to high affinity antibody with time but also with the production of low levels of antibody. It is suggested that these quantitative and qualitative defects in the antibody response may lead to increased susceptibility to immune complex disease.