How B cells and dendritic cells may cooperate in antigen purification

The specificity of the immunological responses is achieved through the cooperation of three classes of cells: B and T lymphocytes, and dendritic cells (DCs). A critical, intensely studied interaction is that between DCs and T cells, during which the DC presents MHC-bound antigenic fragments to the T cell receptor (TCR). There has been recent excitement about the possibility of increasing the signal-to-noise ratio in the detection of cognate antigen-TCR couples, by the use of kinetic proofreading mechanisms. We examine here the signal-to-noise problem in a broader perspective, and in particular, address the question of possible "antigen purification" mechanisms, prior to their presentation to the T cells. Ways in which the DCs might concentrate, purify and preserve their load of captured antigens are considered: (i) If antigens can be transferred from one DC to another, in such a way that the richer a DC in antigen, the more it captures antigens from other DCs, the antigens may end up concentrated in a small subset of DCs, (ii) antigen purification may be achieved through recycling interactions between DCs and B cells. A DC would transmit to a B cell antigen mixtures, and the DC would recapture only the antigens which can bind to the B cell's antibodies and (iii) dendrites, when they are present, may play an essential role in recapturing the antigens that were used in interactions of DCs with T cells, B cells, or other DCs, thereby reducing antigen losses. More generally, we provide a personal interpretation of cell-to-cell antigen transfers, in terms of a strategy in which there is a progressive emergence, through multiple interactions, of subsets of cells of each type better and better prepared for the subsequent rounds of interactions.