Antigen-specific interaction between T and B cells

It is well known that B cells require T-cell help to produce specific antibody. Classic experiments suggested that antigen-specific helper T cells interact with antigen-specific B cells via an antigen ‘bridge’^1,2, the B cells binding to one determinant on an antigen molecule (the ‘hapten’), while the T cells at the same time recognize another determinant (the ‘carrier’). T-helper cells bind specifically to antigen-presenting cells (APC), which have picked up and processed the appropriate antigen, and this interaction, like the interaction of T-helper cells with specific B cells, is restricted by products encoded by the major histocompatibility complex (MHC)^3–5. Whereas conventional APC such as macrophages display no binding specificity for antigen, B cells have clonally distributed antigen-specific surface immunoglobulin receptors which would be expected to enhance their capacity to present antigen to T cells^6,7. These findings are difficult to reconcile with the simple ‘antigen bridge’ mechanism of interaction, because it is hard to visualize how the bimolecular complex (processed antigen plus MHC molecule) on the APC surface can resemble the trimolecular complex (antigen bound to surface immunoglobulin plus MHC molecule) on the B-cell surface. To address this problem, we have cloned and immortalized human antigen-specific B cells with Epstein–Barr virus (EBV) and analysed their interaction with T-cell clones specific for the same antigen. We report here that surface immunoglobulin is indeed involved in the uptake and concentration of antigen, allowing specific B cells to present antigen to T cells with very high efficiency. However, the antigen must first be internalized and processed by specific B cells and it is then presented to T cells in an MHC-restricted manner indistinguishable from that characteristic of conventional APC.