Control of isotype expression by helper T-cell clones and suppressor cells.

We report here experiments demonstrating the profound influence of T lymphocytes on isotype expression by B lymphocytes. It was shown that in a secondary in vitro response, T helper cells from primed spleen predominantly induced an IgG1 plaque-forming cell (PFC) response, while T helper cells from primed lymph node induced IgG1, IgG2a and IgG2b PFC responses. Under the same experimental conditions, T helper cell clones were able to induce IgG1, IgG2a and IgG2b responses; therefore, T helper cells are not involved in controlling preferential isotype expression. Stimulated spleen cells were shown to contain T suppressor cells which were able to limit the expression of IgG2a and IgG2b responses. Under certain circumstances, IgG1-specific suppressor cells were also demonstrated. A T-cell hybridoma, T2D4, spontaneously produced the IgG-binding factor, thereby suppressing the expression of the three subclasses studied. Exposure of these cells to IgG1 myeloma protein led to selective enhancement for the production of molecules binding to IgG1, and suppression of the IgG1 PFC response. Similar observations were made with IgG2a and IgG2b myeloma proteins, and the specificity of these isotype suppressive factors was demonstrated. The general significance of these observations is discussed.