Genetic analysis of the inheritance of B cell hyperactivity in relation to the development of autoantibodies and glomerulonephritis in NZB x SWR crosses.

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Abstract
Autoimmune NZB mice have a primary B cell abnormality manifested by spontaneous hypersecretion of IgM in short-term cultures. The purpose of this study was to characterize the genes that specify this intrinsic B cell defect and determine their relationship to "autoimmunity" genes. The increase in IgM secretion was shown to result from two independently segregating genetic traits: a) an increased number of IgM-containing cells, and b) an increased rate of secretion of IgM per cell. In this study, approximately 600 NZB, SWR, F1, F2, and reciprocal back-cross mice were hemisplenectomized at 5 to 6 months of age to determine the number of IgM-containing cells and the secretion of IgM in 4-hr cultures. These animals were followed prospectively for the development of anti-DNA (native and denatured) and anti-red blood cell autoantibodies, and proteinuria, and studied at autopsy for the development of glomerulonephritis. The severity and incidence of renal lesions was influenced to some extent by the presence of B cell hyperactivity. However, a proportion of F2 and backcross progeny mice that did not show B cell hyperactivity eventually developed autoantibodies and autoimmune disease.