Deletion and editing of B cells that express antibodies to DNA.
We previously demonstrated that in mice transgenic for genes coding for an anti-ssDNA autoantibody B cells were functionally inactivated but not physically deleted. We have now extended this model by introducing an arginine into the CDR2 of the heavy chain transgene. This change alters the specificity of the Ab from anti-ssDNA to anti-dsDNA and increases the affinity for ssDNA. Mice carrying this transgene displayed a significant reduction of peripheral B cells and anti-dsDNA B cells were not recovered from the spleens. The remaining B cells escape deletion by revising their Ag receptors in several ways: 1) elimination of the transgenic heavy chain gene via intrachromosomal recombination, followed by rearrangement and expression of endogenous VH genes; 2) ongoing rearrangement of endogenous kappa light chain genes to generate a non-dsDNA-binding Ab; and 3) expression of a rare V lambda gene, V lambda x, to generate a non-DNA-binding Ab.
Chen
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C
Department of Molecular Biology, Princeton University, NJ 08544.
Radic
M Z
MZ
Erikson
J
J
Camper
S A
SA
Litwin
S
S
Hardy
R R
RR
Weigert
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis*; D001402:B-Lymphocytes / Q000276:immunology*; D001666:Binding Sites, Antibody; D017637:Clonal Deletion; D004247:DNA / Q000276:immunology*; D005260:Female; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000502:physiology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D004247:DNA