Study of congenitally immunologic mutant New Zealand mice. V. B cell function of NZB-Xid mice.

NZB mice bearing the CBA/N X chromosome linked defect were generated by repetitive backcrossing and selection of the Xid gene. The male offspring resulting from the cross of NZB with CBA/N were selected as being XidY on the basis of sera IgM and IgG3 levels and responsiveness to DNP-Lys-Ficoll. Following this inbreeding protocol, 6th generation backcross NZB XidY mice were compared to littermate controls with respect to B cell function. Sera immunoglobulin levels of IgG1, IgG2b and IgA were similar in XidY and XY mice. In contrast, levels of IgM and IgG3, from XidY mice were approximately 15% and 50%, respectively, of values found in littermates. Furthermore, XidY 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 Ig bearing cells in Xid 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 XidY mice had virtually no detectable B cell colonies. This data, obtained on significantly inbred XidY NZB mice, suggests that the Xid gene is dominant over several aspects of polyclonal B cell activation in NZB mice and indicates that serial observation of these mice will be valuable in understanding the interactions of genetic immunologic mutations and cellular function in autoimmunity.