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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…

Populations and Evolution · Quantitative Biology 2024-02-15 Bertrand Ottino-Loffler , Gabriel Victora

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…

Populations and Evolution · Quantitative Biology 2015-05-18 Jingshan Zhang , Eugene I. Shakhnovich

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…

Probability · Mathematics 2018-01-04 Irene Balelli , Vuk Milišić , Gilles Wainrib

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…

Cell Behavior · Quantitative Biology 2021-06-21 Stephen Lindsly , Maya Gupta , Cooper Stansbury , Indika Rajapakse

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 affinity of antibodies (Abs) produced in vivo for their target antigens (Ags) is typically well below the maximum affinity possible. Nearly 25 years ago, Foote and Eisen explained how an 'affinity ceiling' could arise from constraints…

Populations and Evolution · Quantitative Biology 2021-02-16 Rajat Desikan , Rustom Antia , Narendra M. Dixit

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…

Populations and Evolution · Quantitative Biology 2022-03-23 Victor Chardès , Massimo Vergassola , Aleksandra M. Walczak , Thierry Mora

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…

Analysis of PDEs · Mathematics 2015-01-28 Vuk Milisic , Gilles Wainrib

B cells signaling in response to antigen is proportional to antigen affinity, a process known as affinity discrimination. Recent research suggests that B cells can acquire antigen in membrane-bound form on the surface of antigen-presenting…

Cell Behavior · Quantitative Biology 2010-03-09 Philippos K. Tsourkas , Subhadip Raychaudhuri

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…

Populations and Evolution · Quantitative Biology 2024-02-02 Federica Ferretti , Mehran Kardar

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.…

Biological Physics · Physics 2007-05-23 Michael Meyer-Hermann , Tilo Beyer

Within the germinal center in follicles, B-cells proliferate, mutate and differentiate, while being submitted to a powerful selection~: a micro-evolutionary mechanism at the heart of adaptive immunity. A new foreign pathogen is confronted…

Probability · Mathematics 2016-02-12 Irene Balelli , Vuk Milisic , Gilles Wainrib

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…

Populations and Evolution · Quantitative Biology 2015-05-11 Connor O. McCoy , Trevor Bedford , Vladimir N. Minin , Philip Bradley , Harlan Robins , Frederick A. Matsen

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…

Biological Physics · Physics 2007-05-23 Michael Meyer-Hermann

B cells receptor (BCR) signaling in response to membrane-bound antigen increases with antigen affinity, a process known as affinity discrimination. We use computational modeling to show that B cell affinity discrimination requires that…

Cell Behavior · Quantitative Biology 2010-12-14 Philippos K. Tsourkas , Wanli Liu , Somkanya C Das , Susan K. Pierce , Subhadip Raychaudhuri

Immune cells learn about their antigenic targets using tactile sense: during recognition, a highly organized yet dynamic motif, named immunological synapse, forms between immune cells and antigen-presenting cells (APCs). Via synapses,…

Biological Physics · Physics 2018-12-12 Miloš Knežević , Shenshen Wang

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…

Molecular Networks · Quantitative Biology 2015-05-05 Tamás Szabados , Gábor Tusnády , László Varga , Tibor Bakács

Among features of real immune responses which occur when antigens invade a body,there are two remarkable features. One is that the amount of antibodies produced in the secondary invasion by the same antigens is more than 10 times larger…

Populations and Evolution · Quantitative Biology 2007-05-23 Mika Yoshida , Kinji Fuchikami , Tatsuya Uezu

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…

Biological Physics · Physics 2007-05-23 Michael Meyer-Hermann

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…

Populations and Evolution · Quantitative Biology 2024-04-25 Saeed Mahdisoltani , Pranav Murugan , Arup K Chakraborty , Mehran Kardar
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