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.