cDNA sequence analysis and characterization of a cytokine-inducing monoclonal antibody derived from autoimmune MRL/MP-lpr/lpr mouse

We have previously reported that a monoclonal antibody 1D11 derived from an autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mouse induced synthesis or increased production of IL-3, IL-6, and TNF-alpha in the IL-3-dependent bone marrow-derived cell line FDC-P2/185-4. In this report, we analyzed a sequence of cDNA encoding the V region of 1D11, and found that VH and VL segments of 1D11 belonged to the J558 and V kappa 21 family, respectively. The nucleotide sequence of 1D11 in the VH segment was highly homologous to that of AM9, a monoclonal RF derived from MRL/lpr mouse, and the only difference was the replacement of 3 nucleotides in the framework region 1 (FR1). However, the deduced amino acid sequence of 1D11 was identical to that of AM9. In contrast with the VH segment, the sequences of the VL regions of these two antibodies were quite different from each other; 1D11 showed a 3 base deletion in the FR2 and a 24 base insertion in the FR3 compared with AM9. At present, the mechanisms of such insertions or deletions in the FRs of autoantibodies are almost unknown. It is generally accepted that the differences in specificity and affinity of these autoantibodies depend on differences of CDR sequence. However, it is possible that not only CDRs but also FRs of autoantibodies play a critical role in pathogenicity and/or specificity in autoimmune diseases