Chemical and serologic characterization of human lambda VIII light chains.
The primary structural features and serologic properties of a newly recognized human lambda light (L) chain V region subgroup (V lambda VIII) were elucidated through study of two monoclonal L chains, Bence Jones proteins HAG and BIV. The V region amino acid sequences of these components were highly homologous to each other and to that deduced from the prototypic V lambda VIII cDNA, Humla8f10, which encodes the L chains of the IgM lambda rheumatoid factor HAF10. Proteins HAG and BIV could be classified as members of the V lambda VIII subgroup and distinguished from L chains of the V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI subgroups on the basis of amino acid sequence. In addition to distinctive residues found within the V lambda gene-encoded portion of the molecules, L chains HAG, BIV, and HAF10 contained remarkably different second complementarity-determining regions (CDR2) that consisted of 11 residues, rather than the seven typically found among members of the other five V lambda subgroups. This elongated structure would presumably impart to the ligand-binding site of lambda VIII molecules a markedly different canonical structure compared with those of lambda I, lambda II, lambda III, lambda IV, and lambda VI L chains. By using Bence Jones protein HAG as an immunogen, we obtained polyclonal and monoclonal anti-V lambda VIII subgroup-specific Abs that were used to identify and quantify lambda VIII-related molecules in normal and pathologic states. Among the Ig lambda components present in the serum of normal individuals, approximately 3% had lambda VIII L chains, a frequency comparable to that found among monoclonal Ig lambda proteins or surface(s) Ig lambda+ cells obtained from patients with malignant plasma cell- or B cell-related disorders, respectively. In contrast, lambda VIII L chains were detected on approximately 19% of monoclonal IgM lambda rheumatoid factors produced by B cell lines established from PBLs or synovial cells from patients with rheumatoid arthritis. The results of our studies provide new information on the structural and immunochemical features of lambda VIII L chains and the possible functional importance of the human V lambda VIII subgroup.
Solomon
A
A
Department of Medicine, University of Tennessee Medical Center/Graduate School of Medicine, Knoxville 37920.
Weiss
D T
DT
Murphy
C
C
Fu
S M
SM
Robbins
D L
DL
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001536:Bence Jones Protein / Q000737:chemistry / Q000276:immunology; D016384:Consensus Sequence; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry* / Q000276:immunology*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D007146:Immunoglobulin lambda-Chains; D001536:Bence Jones Protein