Analysis of central B cell tolerance in autoimmune-prone MRL/lpr mice bearing autoantibody transgenes.
The effect of the autoimmune prone MRL/lpr (H-2k) genetic background on central B cell tolerance was studied in mice bearing 3-83 (anti-H-2Kk) Ig heavy and light chain transgenes. B cells bearing the dominant, transgene-encoded anti-H-2Kk specificity were tolerized appropriately on the MRL/lpr genetic background. Nevertheless, mice developed disease traits characteristic of the MRL/lpr strain, including lymphadenopathy and elevated levels of IgG dsDNA autoantibodies. Two transgenic lines were examined in this analysis: 3-83 mu delta, which expresses IgM and IgD forms of the 3-83 Ab, and Tol 1, which expresses only the IgM form of 3-83. The results obtained differed somewhat between the two transgenic lines. Crosses using 3-83 mu(delta) mice never demonstrated any defects in B cell self-tolerance to H-2Kk. Similarly, no Kk autoantibody production was seen in Tol 1 mice that were backcrossed onto the MRL/lpr genetic background and maintained in a specific pathogen-free facility. However, a subset of Tol 1/MRL/lpr mice that were housed in a conventional mouse facility demonstrated significant transgene-derived anti-Kk autoantibodies. Overall, these results suggest that there is no general defect in central B cell tolerance in MRL/lpr mice, despite their defect in the fas gene. These findings suggest similarities between the MRL/lpr T and B cell systems, because both fail to manifest clear central tolerance defects, but they nevertheless promote hyperplasia and autoimmunity in the peripheral immune system.
Rubio
C F
CF
Division of Basic Science, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Kench
J
J
Russell
D M
DM
Yawger
R
R
Nemazee
D
D
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001323:Autoantibodies / Q000235:genetics*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D003433:Crosses, Genetic; D004247:DNA / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics; D007108:Immune Tolerance; D007136:Immunoglobulins / Q000097:blood; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D019076:Transgenes / Q000276:immunology*
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D007136:Immunoglobulins; D004247:DNA