Related papers: Quantifying evolutionary constraints on B cell aff…
To recognize pathogens, B and T lymphocytes are endowed with a wide repertoire of receptors generated stochastically by V(D)J recombination. Measuring and estimating the diversity of these receptors is of great importance for understanding…
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…
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 are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such…
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…
The evolution of the adaptive immune system is characterized by changes in the relative abundances of the B- and T-cell clones that make up its repertoires. To fully capture this evolution, we need to describe the complex dynamics of 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…
The efficient recognition of pathogens by the adaptive immune system relies on the diversity of receptors displayed at the surface of immune cells. T-cell receptor diversity results from an initial random DNA editing process, called VDJ…
B cells develop high affinity receptors during the course of affinity maturation, a cyclic process of mutation and selection. At the end of affinity maturation, a number of cells sharing the same ancestor (i.e. in the same "clonal family")…
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…
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…
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…
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…
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…
The human immune system depends on a highly diverse collection of antibody-making B cells. B cell receptor sequence diversity is generated by a random recombination process called "rearrangement" forming progenitor B cells, then a Darwinian…
Fundamental to quantitative characterization of the B cell receptor repertoire is clonal diversity - the number of distinct somatically recombined receptors present in the repertoire and their relative abundances, defining the search space…
One of the key phenomena in the adaptive immune response to infection and immunization is affinity maturation, during which antibody genes are mutated and selected, typically resulting in a substantial increase in binding affinity to the…
Stochastic models of sequential mutation acquisition are widely used to quantify cancer and bacterial evolution. Across manifold scenarios, recurrent research questions are: how many cells are there with $n$ alterations, and how long will…
Microbiological systems evolve to fulfill their tasks with maximal efficiency. The immune system is a remarkable example, where self-non self distinction is accomplished by means of molecular interaction between self proteins and antigens,…
The human body is able to generate a diverse set of high affinity antibodies, the soluble form of B cell receptors (BCRs), that bind to and neutralize invading pathogens. The natural development of BCRs must be understood in order to design…