Expression of an anti-DNA-associated VH gene in immunized and autoimmune mice.
The J558 family BW-16 VH gene is closely associated with the autoimmune response to DNA of lupus-prone mice. We have followed the expression of VHBW-16-encoded heavy chains in cDNA libraries prepared from unmanipulated normal (C3H, AKR) and autoimmune (New Zealand Black/New Zealand White F1) mice, and from mice immunized with a highly immunogenic peptide/DNA complex. The prevalence, clonal heterogeneity, and structural properties (somatic mutation, complementarity-determining region 3 composition) of these H chains were investigated, and the DNA affinity of VHBW-16-encoded hybridoma mAb was measured in solution. We find that H chains encoded by VHBW-16 are very rare in Igs of normal mice, but increase significantly in peptide/DNA-immunized mice, and dramatically in diseased mice. The experimentally induced VHBW-16-encoded H chains are clonally restricted, somatically mutated, partly switched from IgM to IgG, and give rise to anti-DNA Abs with low affinity. In contrast, the VHBW-16-encoded H chains from diseased New Zealand Black/New Zealand White mice are clonally heterogeneous, exclusively of the IgG isotype, and produce high affinity anti-DNA autoantibodies. We conclude that the experimentally induced and spontaneous immune responses to DNA are qualitatively similar, but quantitatively different, and may truly reflect the principles of self immunologic tolerance.
Ash-Lerner
A
A
Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Ginsberg-Strauss
M
M
Pewzner-Jung
Y
Y
Desai
D D
DD
Marion
T N
TN
Eilat
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics*; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D000915:Antibody Affinity; D001483:Base Sequence; D004247:DNA / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D005787:Gene Frequency / Q000276:immunology; D005803:Genes, Immunoglobulin; D005854:Germ Cells / Q000276:immunology; D006825:Hybridomas / Q000737:chemistry; D007114:Immunization; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008814:Mice, Inbred NZB; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D010455:Peptides; D004247:DNA