Myeloma Cell Immunoglobulin Expression during in vivo Growth in Diffusion Chambers: Evidence for Repetitive Cycles of Differentiation

Abstract

Abstract The DNP-binding BALB/c plasmacytoma MOPC-315 undergoes repetitive cycles of differentiation of immunoglobulin expression when serially passaged at 10-day intervals in normal syngenic mice. Within 24 hr of implantation of MOPC-315 cells in i.p. diffusion chambers there is a preferential loss of cells which: a) secrete IgA paraprotein, b) have large amounts of cell surface membrane localized IgA paraprotein, and c) morphologically have a plasmacytic appearance. In addition, myeloma stem cells capable of forming macroscopic splenic colonies following i.v. injection not only survive implantation preferentially, but they also increase in number sooner than any other measured myeloma cell subset. Following the stem cell increase there is a period of progressive increase in the number of myeloma cells with cell surface membrane localized immunoglobulin, and this is followed by an increase in the number of myeloma cells which secrete the homogeneous immunoglobulin. These observations demonstrate that marked changes in the frequency and absolute numbers of myeloma cell subsets occur following implantation in normal syngenic hosts. It is also clear that the changes observed during the initial 7 to 10 days of growth would not have been detected without the DNP-binding property of MOPC-315 used in combination with diffusion chambers which permit sequential recovery of all the surviving cells and their progeny. We interpret our data as indicating linear maturation of the surviving MOPC-315 cells and their progeny, and raise the possibility that this variation in immunoglobulin expression may have fundamental implications for the idiotype-specific suppression of myeloma cell grafts achieved by immunization with purified homologous myeloma immunoglobulin.