Specificity repertoire of lymphocytes from multiple myeloma patients. I. High frequency of B cells specific for idiotypic and F(ab?)2-region determinants on immunoglobulin

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Abstract
The specificity repertoire of B lymphocytes from 14 multiple myeloma patients has been studied using the technique of Epstein-Barr virus (EBV) transformation of peripheral blood lymphocytes (PBL) coupled with clonal analysis by limiting dilution. We find that up to 100% of the B cells from myeloma patients undergoing EBV transformation secrete IgM specific for determinants on the F(ab′)2 region of autologous and/or heterologous monoclonal immunoglobulin. In normal individuals 0.02–0.73% of the transformed B cells secrete IgM specific for F(ab′)2 determinants. Two patients with monoclonal gammopathy of undetermined significance had only a weak reactivity to F(ab′)2 fragments. The number of anti-F(ab′)2 B cells was up to 145-fold greater in patients than in normal donors. The majority of antibodies from patient clones recognized determinants shared among 3–12 different F(ab′)2 fragments, whereas those originating from normal donor B cells saw determinants expressed on only one or two of the panel of test F(ab′)2 fragments. There was a preference for autologous M components and a high proportion of antiidiotypic reactivity in five of eight patients so analyzed. We speculate that these findings indicate the existence of an anti-F(ab′)2 immunoregulatory network mediating patient immunodeficiency, thereby creating an abnormality that may enable the progression of multiple myeloma.