A stochastic model of B cell affinity maturation and a network model of immune memory

Abstract

Many events in the vertebrate immune system are influenced by some element of chance. The objective of the present work is to describe affinity maturation of B lymphocytes (in which random events are perhaps the most characteristic), and to study a possible network model of immune memory. In our model stochastic processes govern all events. A major novelty of this approach is that it permits studying random variations in the immune process. Four basic components are simulated in the model: non-immune self cells, nonself cells (pathogens), B lymphocytes, and bone marrow cells that produce naive B lymphocytes. A point in a generalized shape space plus the size of the corresponding population represents nonself and non-immune self cells. On the other hand, each individual B cell is represented by a disc that models its recognition region in the shape space. Infection is simulated by an "injection" of nonself cells into the system. Division of pathogens may instigate an attack of naive B cells, which in turn may induce clonal proliferation and hypermutation in the attacking B cells, and which eventually may slow down and stop the exponential growth of pathogens. Affinity maturation of newly produced B cells becomes expressed as a result of selection when the number of pathogens decreases. Under favorable conditions, the expanded primary B cell clones may stimulate the expansion of secondary B cell clones carrying complementary receptors to the stimulating B cells. Like in a hall of mirrors, the image of pathogens in the primary B cell clones then will be reflected in secondary B cell clones. This "ping-pong" game may survive for a long time even in the absence of the pathogen, creating a local network memory. This memory ensures that repeated infection by the same pathogen will be eliminated more efficiently.