Related papers: Optimality of mutation and selection in germinal c…
Affinity maturation of antibodies during immune responses is achieved by multiple rounds of somatic hypermutation and subsequent preferential selection of those B cells that express B cell receptors with improved binding characteristics for…
A central feature of vertebrate immune response is affinity maturation, wherein antibody-producing B cells undergo evolutionary selection in microanatomical structures called germinal centers, which form in secondary lymphoid organs upon…
We analyze the interactions between division, mutation and selection in a simplified evolutionary model, assuming that the population observed can be classified into fitness levels. The construction of our mathematical framework is…
B cells and the antibodies they produce are vital to health and survival, motivating research on the details of the mutational and evolutionary processes in the germinal centers (GC) from which mature B cells arise. It is known that B cells…
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…
In order to target threatening pathogens, the adaptive immune system performs a continuous reorganization of its lymphocyte repertoire. Following an immune challenge, the B cell repertoire can evolve cells of increased specificity for the…
During germinal center reactions the appearance of two specific zones is observed: the dark and the light zone. Up to now, the origin and function of these zones are poorly understood. In the framework of a stochastic and discrete model…
The antibody repertoire of each individual is continuously updated by the evolutionary process of B cell receptor mutation and selection. It has recently become possible to gain detailed information concerning this process through…
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.…
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…
The specific morphology of germinal centers is analyzed in the context of the optimization of the humoral immune response. The relevance of dark and light zones for the affinity maturation process is investigated in the framework of a…
Lymphocyte selection is a fundamental operation of adaptive immunity. In order to produce B-lymphocytes with a desired antigenic profile, a process of mutation-selection occurs in the germinal center, which is part of the lymph nodes. We…
Affinity Maturation (AM) is the process through which the immune system is able to develop potent antibodies against new pathogens it encounters, and is at the base of the efficacy of vaccines. At its core AM is analogous to a Darwinian…
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…
A persistent public health challenge is finding immunization schemes that are effective in combating highly mutable pathogens such as HIV and influenza viruses. To address this, we analyze a simplified model of affinity maturation, the…
A fundamental question in biology is how cell populations evolve into different subtypes based on homogeneous processes at the single cell level. Here we show that population bimodality can emerge even when biological processes are…
We study the maturation of the antibody population following primary antigen presentation as a global optimization problem. Emphasis is placed on the trade-off between the safety of mutations that lead to local improvements to the…
When our immune system encounters foreign antigens (i.e., from pathogens), the B cells that produce our antibodies undergo a cyclic process of proliferation, mutation, and selection, improving their ability to bind to the specific antigen.…
We present a model that considers the maturation of the antibody population following primary antigen presentation as a global optimization problem. The trade-off that emerges from our model describes the balance between the safety of…
We show how concepts from statistical physics, such as order parameter, thermodynamic limit, and quantum phase transition, translate into biological concepts in mutation-selection models for sequence evolution and can be used there. The…