IMMUNOGLOBULIN CLASS SWITCH FROM IGA1 TO IGG2 AND SIMULTANEOUS ASSOCIATION WITH BENCE-JONES PROTEINURIA IN THE ESCAPE PHASE IN A MYELOMA PATIENT TREATED WITH INTERFERON-ALPHA

Immunoglobulin (Ig) class switch from alpha 1 to gamma 2 associated wi th kappa-type Bence Jones proteinuria was evident in the escape phase of an IgA1 myeloma patient treated with interferon alpha (IFN alpha). The additional M-protein, IgG2-kappa, level rapidly increased and was associated with Bence Jones proteinuria, whereas monoclonal IgA1-kappa progressively declined. The N-terminal 21 amino acid sequences of the kappa-chains of monoclonal IgA1, IgG2 and the Bence Jones protein wer e the same. The N-terminal 15 amino acid sequence of the gamma 2-chain was identical to that of the alpha 1-chain. Based on these findings, the IgA1 myeloma cells underwent a class switch in CH gene expression from alpha 1 to gamma 2 with cell differentiation in vivo. The mechani sm of the Ig class switching is discussed from three points of view: ( 1) Increase in immature and plasmablastic myeloma cells in the escape phase is susceptible to Ig class switching by the T-cell-derived cytok ines. (2) We presumed that administered IFN alpha increased the amount s of secreted IFN gamma from the Th1 cells. (3) Due to a large quantit y of IFN gamma, an inducer of C gamma 2 germline transcript, Ig class switching occurred stepwise from the alpha 1 constant region gene to t he next 3'CH gamma 2 gene.