Effects of the motheaten gene on murine B-cell production

The rapidly fatal autoimmune disease in the mutant mouse known as motheaten is caused by an autosomal recessive gene and is characterized by hypergammaglobulinemia and autoantibody production, among other defects. The cellular kinetics of B-cell maturation were investigated in three-week-old motheaten mice and their normal littermates to determine whether any abnormality in cell production of the B lineage could be correlated with B-cell hyperactivity. The production rates and renewal times of newly produced bone marrow, splenic small B-lymphocytes, and splenic plasma cells were examined by in vivo tritiated-thymidine administration using a pulse-chase protocol and radioautography of immunofluorescence-stained cells. Because small B-lymphocytes in both organs were produced at comparable rates in the mutant mice and in their normal littermates, primary B-cell production was unaffected in the mutant mice. In contrast, splenic plasma cells were produced 10-30 times faster in motheaten mice than in normal mice. The enhanced rate of plasma cell production in motheaten mice could be correlated with a concurrent increased loss of labeled large B-lymphocytes, presumably rapidly dividing activated B cells. Thus, the excessive antibody production in motheaten mice may be reflected by the increased plasma cell production.