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Molecular heterogeneity of auto‐anti‐idiotypic antibodies in MLR‐lpr/lpr mice

The VH and Vx gene families expressed by 20 monoclonal auto‐anti‐idiotypes (Ab2) derived from unmanipulated MLR‐lpr/lpr mice were determined by Northern blotting. Complete variable region sequences of six Ab2, along with three additional Vx‐JH Ab2 sequences, were obtained. These auto‐anti‐idiotypes arose spontaneously in the animals, and they bound specifically to an idiotypic determinant (ld/r) on mAb 28/12, a monoclonal IgG2b MLR‐lpr/lpr anti‐small nuclear ribonucleoprotein antibody. The 16 Ab2 heavy chains belonged to 7 different VH gene families, and the 10 Ab2 light chains were derived from 8 Vx families. The light chains of two Ab2 were ≈99% identical; the remaining variable region sequences were highly heterogeneous. There was no correlation between primary amino acid sequence of either heavy or light chain and idiotypic properties of the auto‐anti‐idiotypes. Six Ab2 used VH or Vx genes that are identical to known germ‐line genes. A high proportion of the spontaneous auto‐anti‐idiotypes was shown to have autoantibody activity (anti‐DNA, anti‐ribonucleoprotein), or specific binding reactions with lipopolysaccharide of Salmonella RE, or both properties. The structural diversity of spontaneous MLR‐lpr/lpr auto‐anti‐idiotypes differs sharply from the structural homogeneity reported for Ab2 induced in normal animals against syngeneic Ab1. Our results suggest that auto‐anti‐idiotypes might arise independently of an immunogenic stimulus from an Ab1.