HUMAN T-HELPER CLONES INDUCE IGG PRODUCTION IN A SUBCLASS-SPECIFIC FASHION

The mechanisms governing the induction of IgG subclasses by T-helper cells in humans were investigated. As preliminary bulk-culture experiments had indicated that a direct B cell contact with viable T cells was an essential requirement for optimal IgG subclass production, 256 CD4+ human T cell clones were preactivated with PHA and cultured in direct contact with autologous B cells. These clones induced IgG production in a strikingly subclass-specific fashion. Moreover, the distribution of subclass-specific helper clones was very similar to the IgG subclass profile observed in serum and peripheral lymphoid tissue plasma cells (IgG1 ≈ 60%, IgG2 ≈ 30%, IgG3 ≈ 5-10%, IgG4 ≤ 5%) and unlike that observed in resting B cells (which is IgG1 ≈ 40% and IgG2 ≈ 50%). It would, therefore, seem that a predominance of T cells capable of delivering IgG 1 -specific, as opposed to IgG2-specific, help is an essential factor for the preferential induction of IgG1 antibodies during B cell proliferation and differentiation. There was no relationship between IL2, IL4, IL6, and IFN-γ secreted by the T-helper clones and their IgG subclass induction patterns. In addition, only a few supernatants were able to reproduce the helper effects of the clones themselves. Therefore, direct contact of B cells with helper clones is crucial for IgG-subclass production in humans. © 1992.