Studies on the clonal origin of multiple myeloma. Use of individually specific (idiotype) antibodies to trace the oncogenic event to its earliest point of expression in B-cell differentiation.

Abstract

Ig[immunoglobulin]A myeloma proteins of .kappa.- and .lambda.-types were isolated from 2 patients. These were used to produce and purify anti-idiotype antibodies of both broad (myeloma-related) and narrow (individual myeloma) specificities. The anti-idiotype antibodies were conjugated with fluorochromes and used as immunofluorescent probes to trace in the patients clonal expansion at different levels of B [bone marrow-derived] cell differentiation. B lymphocyte precursors in IgA plasma-cell myelomas were involved in the malignant process. B lymphocytes of the malignant clone included those expressing each of the major H chain isotypes, .mu., .delta., .gamma. and .alpha.. Strong circumstantial evidence was provided that pre-B cell members of the malignant clone were also increased in frequency. T [thymus-derived] cells expressing idiotypic determinants were not detected. The initial oncogenic event may occur in a B stem cell and is not influenced through stimulation by antigen. An interesting association was the increased frequency of related clones of B lymphocytes as detected by their reactivity with anti-idiotype antibodies of broad specificity. Neither plasma cell nor pre B cell members of these related clones were increased in frequency. Anti-idiotype antibodies or helper T cells reactive with myeloma-related idiotypes could be responsible for this phenomenon. Other implications of these findings were discussed. All of the various phenotypes of B lineage malignancies may result from oncogenic processes affecting stem cell targets.