Study of congenitally immunologic mutant New Zealand mice. cell function of NZB-X(id) mice

NZB mice bearing the CBA/N X chromosome linked defect were generated by repetitive backcrossing and selection of the X(id) gene. The male offspring resulting from the cross of NZB with CBA/N were selected as being X(id)Y on the basis of sera IgM and IgG₃ levels and responsiveness to DNP-Lys-Ficoll. Following this inbreeding protocol, 6th generation backcross NZB X(id)Y mice compared to littermate controls with respect to B cell function. Sera immunoglobulin levels of IgG₁, IgG(2a), IgG(2b) and IgA were similar in X(id)Y and XY mice. In contrast, levels of IgM and IgG₃, from X(id)Y mice were approximately 15% and 50%, respectively of values found in littermates. Furthermore, X(id)Y mice failed to respond to DNP-Lys-Ficoll and had less than 3% splenic Lyb 5.1-bearing cells. Splenic immunoglobulin cell surface profiles, obtained by the fluorescent activated cell sorter, indicated a significant reduction in the frequency of X(id) bearing cells in X(ld) animals. Such profiles were similar to those obtained for spleen cells from reference control CBA/N mice. Finally, an elevated number of splenic, lymph node and bone marrow background and lipopolysaccharide-induced B cell clones in semi-solid phase agar was found in NZB but not C57BL/6, C3H, BALB/c and DBA/2 controls. In contrast, NZB X(id)Y mice had virtually no detectable B cell colonies. This data, obtained on significantly inbred X(id)Y NZB mice, suggests that the X(id) gene is dominant over several aspects of polyclonal B cell activation in NZB mice and indicates that seral observation of these mice will be valuable in understanding the interactions of genetic immunologic mutations and cellular function in autoimmunity.