Genetic regulation of lipopolysaccharide responses in NZB mice.
Several of the autoimmune defects of NZB mice have been linked to chromosome 4 where the Lps gene which regulates B cell activation by bacterial lipopolysaccharide (LPS) is found. Thus, studies of an NZB.Lpsd strain may facilitate functional analysis of B cell hyperactivity. To develop NZB.Lpsd mice, the Lpsd mutation of C57BL/10ScN mice was further characterized by studying the influence of Lpsd on LPS-induced spleen cell proliferation colony-stimulating factor (CSF) production, and B cell colony-forming unit (CFU-B) proliferation in (C57BL/10SnJ X C57BL/10ScN) F1 X C57BL/10ScN mice. Twenty-one of 27 backcross offspring demonstrated concordance of results in the three assays indicating common genetic regulation of these traits. Subsequently, the Lps allele of NZB mice was characterized by determining the mitogen responsiveness, CSF production and CFU-B proliferation of (NZB X C57BL/10ScN) F1 X C57BL/10ScN mice. In addition, concordance of assortment of the C57BL/10ScN Mupb allele and LPS unresponsiveness was verified. Results of these assays were concordant in 12 of 14 backcross mice, indicating that NZB LPS responsiveness is also regulated by a gene or closely linked set of genes on chromosome 4. Further, the LPS responsiveness of homozygous fifth backcross NZB.Lpsd mice was significantly diminished compared to that of NZB mice. Interestingly, the hypergammaglobulinemia and anti-DNA antibody levels in 6-month-old Lpsd mice did not differ from those of NZB mice despite the absence of LPS-responsive CFU-B.
Bearer
E A
EA
Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis.
Ansari
A A
AA
Gershwin
M E
ME
D000818:Animals; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D003433:Crosses, Genetic; D005838:Genotype; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB / Q000235:genetics* / Q000276:immunology; D009154:Mutation
D003115:Colony-Stimulating Factors; D008070:Lipopolysaccharides