Anti-idiotypic regulation of IgA expression in myeloma cells.

MOPC-315 (alpha lambda 2) is a BALB/c plasmacytoma that produces an anti-TNP antibody (M315). In addition to being secreted M315 is also expressed on the surface membranes of MOPC-315 cells. In the present studies an in vitro-adapted line of MOPC-315 was used to study the effect of affinity-purified, isologous anti-idiotypic antibodies (a-Id315) and idiotype-specific T cells on M315 expression. We observed that both monoclonal and polyclonal a-Id315 mediated a reversible clearance of surface membrane M315 but did not influence M315 secretion or MOPC-315 growth even when the myeloma cells were cultured in the continuous presence of a-Id315 for three weeks. Clearance of surface M315 was rapid, reversible, and a-Id315 dose-dependent. M315:a-Id315 complexes were shed from MOPC-315 cells in the form of microscopic membranous vesicles and a-Id315 was consumed in the process. Protein synthesis was required for re-expression of surface M315 only if a presynthesized internal pool of M315 had previously been depleted. In contrast, idiotype-specific T cells mediated specific inhibition of M315 secretion without influencing surface M315 expression. Although the anti-idiotypic antibodies and the anti-idiotypic T-cells are both directed to the surface membrane immunoglobulin on the cloned B cell, the anti-idiotypic antibodies regulate surface membrane expression of immunoglobulin while the anti-idiotypic T-cells regulate secretion of immunoglobulin. These observations support the view that in idiotype regulation, surface membrane immunoglobulin molecules function as a focusing device for regulatory effectors which actually determine the quality of the effect achieved.