V-GENE-SEQUENCES OF HUMAN ANTI-SSDNA ANTIBODIES SECRETED BY LUPUS-DERIVED CD5-NEGATIVE B-CELL HYBRIDOMAS

V gene sequences encoding two lupus-derived human monoclonal IgMk anti -ssDNA antibodies (2F7 and 1A6) and CD5 mRNA expression by the corresp onding hybridomas were investigated. Both antibodies displayed V gene sequences nearly in germline configuration compared with their putativ e germline counterparts. It appeared that 2F7 used hv3019b9/HUD-3/J(H) 6 and 12La/J(k)2, while 1A6 utilized HHG19/D31-HUD-3/J(H)2 and Humkv32 8h5/J(k)1. Assessment of R/S mutation ratios suggested that 2F7 and 1A 6 have not undergone the antigen-driven somatic mutation. The HCDR3 fe aturing arginine appeared to be important in determining the anti-ssDN A specificity. CD5 mRNA was negative in both hybridomas. Since 2F7 was previously shown to be monospecific and of high affinity, these resul ts provide the molecular basis of such unique immunochemical character istics of the IgM anti-ssDNA antibody. Germline V genes and N sequence s may be selected to confer such anti-ssDNA specificity during V gene rearrangement, which might involve CD5-negative B cells. (C) 1996 Acad emic Press, Inc.