An analysis of B cell selection mechanisms in germinal centers

The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strengt...

We discuss the origin of two classes of germinal centers that have been observed during humoral immune responses: Some germinal centers develop very well and give rise to a large number of high affinity antibody producing plasma cells. Other germinal center reaction are very weak and the output production is practically absent. We propose an explanation for this nearly all-or-none behavior of germinal center reactions: The affinity of the seeder B-cells to the antigen is the ...

The mammalian adaptive immune system has evolved over millions of years to become an incredibly effective defense against foreign antigens. The adaptive immune system's humoral response creates plasma B cells and memory B cells, each with their own immunological objectives. The affinity maturation process is widely viewed as a heuristic to solve the global optimization problem of finding B cells with high affinity to the antigen. However, memory B cells appear to be purposely...

A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in substructures of lymph nodes, called germinal centers. While it has been shown that the median B cell affinity dependably increases over the course of maturation, the exact logic behind this evolution remains vague. Three potential selection methods include encouraging the reproduction of high affinity cells (``birth/positive selection''...

How does immune system evolve functional proteins - potent antibodies - in such a short time? We address this question using a microscopic, protein-level, sequence-based model of humoral immune response with explicitly defined interactions between Immunoglobulins, host and pathogen proteins. Potent Immunoglobulins are discovered in this model via clonal selection and affinity maturation. Possible outcomes of an infection (extinction of cells, survival with complete eliminatio...

Germinal centres are anatomically defined lymphoid organ structures that mediate B cell affinity maturation and affect the quality of humoral immune responses. Mathematical models based on differential equations or agent-based simulations have been widely used to deepen our understanding of the cellular and molecular processes characterizing these complex dynamic systems. Along with experimental studies, these tools have provided insights into the spatio-temporal behavior of ...

We introduce a new model for the dynamics of centroblasts and centrocytes in a germinal center. The model reduces the germinal center reaction to the elements considered as essential and embeds proliferation of centroblasts, point mutations of the corresponding antibody types represented in a shape space, differentiation to centrocytes, selection with respect to initial antigens, differentiation of positively selected centrocytes to plasma or memory cells and recycling of cen...

Mechanisms of immunity, and of the host-pathogen interactions in general are among the most fundamental problems of medicine, ecology, and evolution studies. Here, we present a microscopic, protein-level, sequence-based model of immune system, with explicitly defined interactions between host and pathogen proteins.. Simulations of this model show that possible outcomes of the infection (extinction of cells, survival with complete elimination of viruses, or chronic infection w...

The adaptive immune system constantly remodels its lymphocyte repertoire for better protection against future pathogens. Its ability to improve antigen recognition on the fly relies on somatic mutation and selective expansion of B lymphocytes expressing high-affinity antigen receptors. However, this Darwinian process inside an individual appears ineffective, hitting a modest ceiling of antigen-binding affinity. Experiment began to reveal that evolving B cells physically extra...

We introduce a novel, multi-scale model for affinity maturation, which aims to capture the intra-clonal, inter-clonal and epitope-specific organization of the B cell population in a germinal center. We describe the evolution of the B cell population via a quasispecies dynamics, with species corresponding to unique B cell receptors (BCRs), where the desired multi-scale structure is reflected on the mutational connectivity of the accessible BCR space, and on the statistical pro...