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

T. Koizumi, A. Puccetti, P. Migliorini, K. J. Barrett, R. S. Schwartz

Research output: Contribution to journalArticlepeer-review

Abstract

The V(H) and V(κ) 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(κ)-J(H) 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 IgG(2b) MLR-lpr/lpr anti-small nuclear ribonucleoprotein antibody. The 16 Ab2 heavy chains belonged to 7 different V(H) gene families, and the 10 Ab2 light chains were derived from 8 V(κ) 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 V(H) or V(κ) 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.

Original languageEnglish
Pages (from-to)2185-2193
Number of pages9
JournalEuropean Journal of Immunology
Volume21
Issue number9
Publication statusPublished - 1991

ASJC Scopus subject areas

  • Immunology

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