Serologically defined V region subgroups of human lambda light chains
Solomon, A.; Weiss, D.T.
Journal of Immunology 139(3): 824-830
1987
ISSN/ISBN: 0022-1767 PMID: 3110284 Document Number: 303361
The availability of numerous antisera prepared against .lambda.-type Bence Jones proteins and .lambda. chains of known amino acid sequence has led to the differentiation and classification of human .lambda. light chains into one of five V.lambda. subgroups. The five serologically defined subgroups, V.lambda.I, V.lambda.II, V.lambda.III, V.lambda.IV, and V.lambda.VI, correspond to the chemical classification that is based on sequence homologies in the first framework region (FR1). Proteins designated by sequence as .lambda.V react with specific anti-.lambda.II antisera and are thus included in the V.lambda.II subgroup classification. The isotypic nature of the five V.lambda. subgroups was evidenced through analyses of .lambda.-type light chains that were isolated from the IgG of normal individuals. Based on analyses of 116 Bence Jones proteins, the frequency of distribution of the .lambda.I, .lambda.II/V, .lambda.III, .lambda.IV, and .lambda.VI proteins in the normal .lambda. chain population is estimated to be 27%, 37%, 23%, 3%, and 10%, respectively. This distribution of V.lambda. subgroups was comparable to that found among 82 monoclonal Ig.lambda. proteins. Considerable V.lambda. intragroup antigenic heterogeneity was also apparent. At least two sub-subgroups were identified among each of the five major V.lambda. subgroups, implying the existence of multiple genes in the human V.lambda. genome. The V.lambda. classification of 54 Ig.lambda. proteins obtained from patients with primary or multiple myeloma-associated amyloidosis substantiated the preferential association of .lambda.VI light chains with amyloidosis AL and the predominance of the normally rare V.lambda.VI subgroup in this disease.