An unsolved problem of the clonal selection theory and the model of an oligomeric B-cell antigen receptor

The B-cell antigen receptor (BCR) plays a central role in the development, survival and activation of B lymphocytes. As the pre-BCR, it controls allel ic exclusion of heavy chains and the expansion of pre-B cells. As the BCR, it controls the positive and negative selection of immature B cells as well as the survival and activation of mature B cells. Recent studies of recept ors have shown that it is the Ligand that brings them into the conformation necessary for signaling. How the multiple and structurally diverse antigen s could fulfill this task for the BCR is unknown, and we regard this as an unsolved problem of Burnet's clonal selection theory. This question and our recent biochemical studies lead us TO propose a new moder for the BCR, acc ording to which the BCR exists as a precise oligomeric complex on the B-cel l surface. In this form, it can signal positive selection and survival of B cells. Binding to self- or foreign antigen results in a distortion of the oligomeric complex that gives the signal for negative selection of immature and activation of mature B cells.