STUDY OF CONGENITALLY IMMUNOLOGIC MUTANT NEW ZEALAND MICE: V. B CELL FUNCTION OF NZB‐Xld MICE

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Abstract
Summary: NZB mice bearing the CBA/N X chromosome linked defect were generated by repetitive backcrossing and selection of the Xld gene. The male offspring resulting from the cross of NZB with CBA/N were selected as being XldY on the basis of sera IgM and IgG3 levels and responsiveness to DNP‐Lys‐Ficoll. Following this inbreeding protocol, 6th generation backcross NZB XldY mice were compared to littermate controls with respect to B cell function. Sera immunoglobulin levels of IgG1, IgG2a, IgG2b and IgA were similar in XldY and XY mice. In contrast, levels of IgM and IgG3, from XldY mice were approximately 15% and 50%, respectively, of values found in littermates. Furthermore, XldY 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 Xld 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 XldY mice had virtually no detectable B cell colonies. This data, obtained on significantly inbred XldY 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.