Introduction
The VH and V, 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 V,-JH Ab2 sequences, were obtained. These auto-anti-idiotypes arose spontaneously in the animals, and they bound specifically to an idiotypic determinant (Id/r) on mAb 28/12, a monoclonal IgGzb 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 V, 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 V, 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, antiribonucleoprotein) , 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 Abl. Our results suggest that auto-anti-idiotypes might arise independently of an immunogenic stimulus from an Abl.
Antibodies that can recognize idiotypes of autologous or syngeneic Ig auto-anti-idiotypes occur in pooled normal y-globulin [l, 21, in allergic [3,4], infectious [5, 61, and autoimmune diseases [7-111, and as a distinctive component of the B cell repertoire of newborn mice . By contrast with the abundance of structural data on idiotypes (Abl) [13-201, very little is known about the structures of (Ab2) [21-231. Thus far, V region sequences of autoanti-idiotypes that arise in the absence of deliberate immunization with exogenous immunogens ("spontaneous" auto-anti-idiotypes) have not been reported.
In this report we show that the H and L chain V regions of auto-anti-idiotypes obtained from unmanipulated MLRlpr/lpr mice are structurally diverse, and that they can be encoded by unmutated germ-line Vgenes. The heterogeneity of these spontaneous auto-anti-idiotypes from autoimmune mice contrasts sharply with the homogeneity of anti-idiotypes that have been elicited in normal mice by immunization with syngeneic idiotypes [21-231. Our results suggest that spontaneous auto-anti-idiotypes might originate from immunogenic stimuli that are unrelated to the variable region of Abl.The data support the concept that V regions of apparently unrelated antibodies have the potential to assemble into an idiotypic network [24,25].