The Problem of Antigen Affinity Discrimination in B-Cell Immunology

Abstract

B and T lymphocytes activate the humoral and cellular arms of the adaptive immune system. The adaptive strategy works because receptors of adaptive immune cells can mount an immune response based on their affinity for antigens. Thus, affinity discrimination is central to adaptive immunity and has important biomedical ramifications. Due to its intricate connection to the affinity maturation process, affinity discrimination has a special significance in B-cell-mediated immune response. The role of affinity-matured high-affinity antibodies is increasingly recognized in vaccine development. In this paper, we discuss the recent progress made in mathematical and computational studies to explore the cellular and molecular mechanisms of B-cell affinity discrimination. Formation of B-cell receptor (BCR) oligomers and BCR-lipid rafts, upon antigenic stimulation, emerge to be key factors in B-cell affinity discrimination (at the level of single cells). It also provides a new way of thinking about kinetic proofreading and serial triggering, concepts that have been widely utilized to understand affinity discrimination in adaptive immune cells. Potential future applications of mathematical and computational modeling of affinity discrimination are discussed in the context of autoimmune disorders and vaccine design.