A model system for the analysis of B-cell activation and effector T-cell functions. T cell-dependent B-cell responses facilitated by anti-I-A antibodies.

We have attempted to develop an in vitro system where polyclonal B lymphocyte responses could be induced in ‘antigen-like’ conditions, that is, where surface immunoglobulin-dependant binding mediates interaction with a mitogen. Monoclonal anti-μ and anti-δ antibodies were covalently bound to lipopolysaccharide (LPS) and these complexes were shown to display mitogenic activity. Polyclonal plaque-forming-cell (PFC) responses, however, were diminished in cultures stimulated by anti-μ-LPS (but not by anti-δ-LPS) indicating that ‘anti-μ inhibition’ of terminal B-cell differentiation also applies to ‘specific’ antibody responses. Moreover, the analysis of the functional activity of monoclonal antibodies to major histocompatibility complex (MHC) class II molecules revealed a surprising synergy between low. non-stimulatory concentrations of anti-μ-LPS (but not anti-SdL-LPS) with anti-I-A antibodies. These responses are T-cell dependent and synergy with anti-μ-LPS conjugates can also be obtained with ‘naturally’ activated CD4+ cells isolated from normal donors. A model of molecular and cellular interactions was derived, which accounts for the present findings and is applicable in antigen-dependent lymphocyte collaboration.