Specificities and V genes encoding monoclonal autoantibodies from viable motheaten mice.
Several hundred hybridomas were obtained from 1-2-mo-old viable motheaten (mev) mice. Among the Ig-secreting hybridomas tested, greater than 50% (17/33) exhibited reactivity for autoantigens, supporting the idea that the Ly-1 B cells that predominate in mev mice contain frequent precursors of autoantibody-forming cells. Certain of the specificities of these autoantibodies correlated with the documented pathophysiology of mev mice (antithymocyte, -erythrocyte, -skin, -kidney, and -IgG); others were specific for autoantigens not previously observed in motheaten mice but though to be involved in other autoimmune diseases (e.g., intrinsic factor, transferrin, myelin basic protein, and thyroglobulin). About 2 of 3 (11/17) of the self-reactive antibodies exhibited multispecific binding activity for various autoantigens. Analysis by Northern blotting of the V gene families used in mev autoantibodies showed a random usage of VH families and a biased usage of four Vk gene families. Of 16 autoantibodies tested, 12 used a Vk gene from the Vk1, 4, 10, or 19 families. These patterns of Vk gene usage differ from nonautoimmune control animals. Overall, an immunoregulatory defect operating at a more generalized level than the VH or Vk loci, and due to a single gene mutation, appears to be responsible for the multiple immune abnormalities of mev mice.
Painter
C J
CJ
Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029.
Monestier
M
M
Chew
A
A
Bona-Dimitriu
A
A
Kasturi
K
K
Bailey
C
C
Scott
V E
VE
Sidman
C L
CL
Bona
C A
CA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000276:immunology; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D007135:Immunoglobulin Variable Region