Generation of heavy chain-loss mutants in a B cell hybrid mediated by syngeneic idiotype-specific spleen cells.

Idiotype-specific spleen cells from appropriately primed BALB/c mice cause a marked and irreversible suppression of the membrane and secreted forms of idiotype-positive immunoglobulin (Ig) of an antigen-specific B cell hybrid clone (2C3E1). The suppression of this BALB/c B cell line has been observed in vitro and in vivo, and appears to require intimate contact between effector spleen cells and target 2C3E1 cells. The observed suppression in the 2C3E1 cell line is due to an induced mutation or a selection of pre-existing mutants within the 2C3E1 cell population, because the resultant light and heavy chain-loss variants are phenotypically stable in vitro and in vivo in the absence of any further active suppression. Biochemical analysis of the 2C3E1 cells after this suppression indicates that all of the variants are negative for the production of idiotype-positive Ig. Heavy chain synthesis by the variants is almost totally eliminated, and light chain synthesis is decreased by 10 to 90%. Spleen cells from identically primed nude mice do not induce any alteration in the 2C3E1 cell line, suggesting that induction or selection of the heavy and light chain-loss mutants requires the presence of mature T lymphocytes. The generation of idiotype-negative 2C3E1 variants during the period of tumor growth in the spleen (but not elsewhere) may represent one mechanism by which this tumor escapes the host's immune recognition.