The VH gene sequences of anti‐DNA antibodies in two different strains of lupus‐prone mice are highly related

Abstract The heavy and light chain V region sequences of an IgG anti‐DNA autoantibody (PME77), derived from a lupus‐prone (NZB x NZW)F 1 mouse have been determined by mRNA sequencing. The V x gene segment belongs to the V x 1A gene subgroup and is found in several (NZB x NZW)F 1 and MRL lpr/lpr anti‐DNA antibodies, as well as in other antibodies of unrelated specificities. The V H gene segment appears to represent a unique gene or a subfamily of the large J558 V H gene family of the mouse, and is highly related to a germ‐line sequence of a major anti‐DNA idiotype (H130, IgM) of MRL mice. This anti‐DNA‐related V H segment has not been found, so far, to be expressed in antibodies with specificities for external or synthetic antigens; therefore, expression of such specificities may be regulated by powerful mechanisms of self tolerance in the healthy animal. In addition, both the heavy and light chain of the PME77 IgG antibody were found to contain somatic point mutations with a high ratio of replacement to silent mutations in complementarity determining regions. This IgM to IgG sequence relationship suggests an affinity maturation process, which is driven by the autoantigen.