Characterization of a B cell defect in the NZB mouse manifested by an increased ratio of surface IgM to IgD

In an effort to define the cellular basis of abnormalities in polyclonal B cell activation previously noted in NZB mice, the surface immunoglobulin (sIg) isotypes of spleen cells from NZB mice were examined. After lactoperoxidase-catalyzed radioiodination, the cell surface immunoglobulins were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Spleen cells from 8- to 10-week-old NZB mice were found to have an increased ratio of cell surface IgM/IgD compared to cells from 11 control strains. The altered ratio of sIg isotypes was not a consequence of increased proteolytic activity present in NZB cell suspensions or of the presence of cytophilic antibody or autoantibody. Ontogenetic studies of the sIgM/sIgD (μ/δ) ratio on splenocytes from NZB and BALB/c mice revealed that the former cells had higher μ/δ ratios as early as 2 weeks after birth. By 4 weeks of age the μ/δ ratios were equivalent. Between 4 weeks and 1 year of age, the μ/δ ratios on NZB splenocytes remained constant whereas those on BALB/c splenocytes decreased and reached adult levels at 6 weeks.