Evidence for 65 electrophoretically distinct groups of light chains in BALB/c and NZB myelomas.

Light chains of 426 randomly selected myelomas from BALB/c and NZB mice were characterized by isoelectric focusing (IF) and electrophoresis at pH 3. Approximately 50% of the light chains in each strain were found to have unique electrophoretic properties. The remaining 50% of light chains fell into groups of two or more proteins showing apparent identity. A total of 49 groups of light chains were identified in this way. On the basis of repeat frequencies, the total number of such groups has been estimated to be around 65. Analysis of light chains of known amino acid sequence suggests that many of the "IF-groups" may represent light chains belonging to single V-region subgroups. The large number of unique light chains could represent somatic mutants bearing charge differences from the germ-line-coded sequences or products of a subset of V-genes which are infrequently expressed in myeloma proteins. Comparison of the light chains of BALB/c and NZB myelomas indicated extensive overlap of IF-subgroups in the two strains. One clear difference between the two samples was the presence of three groups of light chains at an unexpectedly high frequency in the BALB/c myelomas. In contrast, no light chains belonging to these groups were found in the NZB myelomas. One of the anomalous groups corresponded to Vk-1A light chains, a subgroup previously shown to be absent in NZB serum light chain IF-profiles. A second group represented at an elevated level included MOPC467, a light chain closely related in sequence to Vk-1A. The third group included ADJPC5 and LPC1. The overrepresentation of these light chain groups in the BALB/c myelomas is not understood. Two light chain-like polypeptides were observed in approximately 3-5% of myelomas in the two mouse strains. It seems likely that in many instances this may be explained by the presence of two cell lines in early generation tumors.