Immunoregulation of Murine Myeloma: Isologous Immunization with M315 Induces Idiotype-Specific T Cells that Suppress IgA Secretion by MOPC-315 Cells in vivo

Abstract

Previous studies demonstrated that MOPC-315 cells enclosed in peritoneal diffusion chambers (DC) in M315-immunized BALB/c mice did not secrete the 2,4,6-trinitrophenyl (TNP)-binding IgA paraprotein (M315). The secretory blockade was: i) idiotype (Id³¹⁵)specific, ii) reversed in vitro after mild pronase treatment, and iii) independent of any effect on the cytologic differentiation of MOPC-315 from lymphocytoid to plasmacytoid cells. In addition to secretory blockade, MOPC-315 cells in M315-immunized hosts exhibited a marked reduction in expression of cell surface M315 (sIgA³¹⁵). Since the alterations in M315 expression occurred across a 0.1-µ Millipore membrane, we proposed that Id³¹⁵-specific, soluble factors contributed to the effector mechanism. In the present studies, Id³¹⁵-specific suppression of M315 secretion was adoptively transferred to normal mice with spleen cells from M315-immunized donors, and the transfer could be abrogated by treatment of the immune spleen cells with heterologous anti-ϑ serum plus complement. Furthermore, in contrast to actively immunized mice, adoptively immunized mice neither developed anti-Id³¹⁵ antibodies nor suppressed sIgA³¹⁵ expression. These findings: i) establish that idiotype-specific suppression of M315 secretion is a process distinct from inhibition of sIgA³¹⁵ expression, ii) demonstrate that secretory blockade of MOPC-315 cells is dependent on Id³¹⁵-specific T cells, and iii) suggest that inhibition of sIgA³¹⁵ expression is dependent on anti-Id³¹⁵ antibodies. The results presented here establish that immunoglobulin expression by MOPC-315 cells is responsive to idiotype-specific T cell regulation as well as the antigen-specific T cell regulation we described earlier. These studies provide further insight into the mechanisms of idiotype-specific regulation of myeloma and may contribute to more complete understanding of T cell-mediated regulation of idiotype expression in non-neoplastic B cells.