Structural and idiotypic characterization of the L chains of human IgM autoantibodies with different specificities.

We have determined the V region amino acid sequence and/or serologic markers (kIIIb, PSL2, and PSL3) of 24 IgM monoclonal autoantibodies with specificities of anti-gamma-globulin (RF), anti-I (cold agglutinin), anti-low density lipoprotein and anti-intermediate filaments. The data emphasize the overwhelming selection of the HumKv325/VkIIIb L chain for this family of autoantibodies. The few amino acid substitutions found within the VL regions were mainly concentrated in the complementarity-determining region 1. JK and CK genes did not show the same pattern of restriction. There is a good correlation between the amino acid sequence and the presence of the kIIIb marker. The idiotypic marker PSL2 was present in 34 out of 35 kIIIb L chains analyzed (97%) and the PSL3 in 27 (80%). Moreover, the hydrophilicity and antigenic profiles of these L chains corroborate the presence of the epitopes detected by the anti-CRI. These results demonstrate a restricted selection of the Vk genes used by a family of self reacting proteins, and an unusual evolutionary conservation of the idiotypic structure that may be involved in the network regulation.