The anti-La response of a single MRL/Mp-lpr/lpr mouse: specificity for DNA and VH gene usage.
Autoantibodies to ribonucleoproteins (RNP) occur prominently in human systemic lupus erythematosus and murine lupus models. In previous studies we demonstrated a relationship in MRL/Mp-lpr/lpr (MRL/lpr) mice between antibodies to Sm, an RNP autoantigen, and antibodies to DNA. Thus, many anti-Sm monoclonals bound DNA and expressed the same V region genes as anti-DNA. In addition, many had multiple VHCDR3 Arg residues suggestive of selection by DNA, and some had somatic mutations suggesting selection for mutant B cells by DNA. To determine whether autoantibodies to other RNP antigens are also associated with the anti-DNA response, we have analyzed the response to the La RNP. Six anti-La B cell hybridomas were generated from a single MRL/lpr mouse. Southern blot analysis of Ig V gene rearrangements and V gene sequences indicated two clonally related pairs, suggesting an oligoclonal response. Antibodies from all six hybridomas bound single-stranded DNA, while antibodies from five hybridomas bound double-stranded DNA. Two hybridomas expressed a VH7183 gene which is used by members of two previously reported anti-DNA clones and two anti-Sm/DNA clones of MRL/lpr origin. These data demonstrate an association between the anti-La and anti-DNA responses in MRL/lpr mice, suggesting that cross-reactive anti-RNP and anti-DNA responses are a general feature of autoimmunity in this lupus model.
Bloom
D D
DD
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599.
St Clair
E W
EW
Pisetsky
D S
DS
Clarke
S H
SH
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000235:genetics; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004247:DNA; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen