An analysis of B cell selection mechanisms in germinal centers

A general criterion is formulated in order to decide if recycling of B-cells exists in GC reactions. The criterion is independent of the selection and affinity maturation process and based solely on total centroblast population arguments. An experimental test is proposed to verify whether the criterion is fulfilled.

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 several possible pathways of zone development during germinal center reactions are investigated. The importance of the zones in the germinal center for affinity maturation, i.e. the process of antibody optimization is discussed.

Our main purpose is to compare classical nonself-centered, two-signal theoretical models of the adaptive immune system with a novel, self-centered, one-signal model developed by our research group. Our model hypothesizes that the immune system of a fetus is capable learning the limited set of self antigens but unable to prepare itself for the unlimited variety of nonself antigens. We have built a computational model that simulates the development of the adaptive immune system...

An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number ...

Some cells have to take decision based on the quality of surroundings ligands, almost irrespective of their quantity, a problem we name "absolute discrimination". An example of absolute discrimination is recognition of not-self by immune T Cells. We show how the problem of absolute discrimination can be solved by a process called "adaptive sorting". We review several implementations of adaptive sorting, as well as its generic properties such as antagonism. We show how kinetic...

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 Darwinian evolutionary process B cells undergo during immunization. The vaccination protocol dictates selection forces that steer affinity maturation to generate antibodies. We focus on determining the optimal selection forces exerted by a gene...

Immunological systems have been an abundant inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing (MONROY, SAAB, GODINEZ, 2004). Simulation systems and mathematical modeling are also beginning use to answer more complex immunological questions as immune memory process and duration of vaccines, where the regulation mechanisms are not st...

We present a new approach to the simulation and analysis of immune system behavior. The simulations that can be done with our software package called SIMMUNE are based on immunological data that describe the behavior of immune system agents (cells, molecules) on a microscopial (i.e. agent-agent interaction) scale by defining cellular stimulus-response mechanisms. Since the behavior of the agents in SIMMUNE can be very flexibly configured, its application is not limited to imm...

System dynamics and agent based simulation models can both be used to model and understand interactions of entities within a population. Our modeling work presented here is concerned with understanding the suitability of the different types of simulation for the immune system aging problems and comparing their results. We are trying to answer questions such as: How fit is the immune system given a certain age? Would an immune boost be of therapeutic value, e.g. to improve the...

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 than that in the primary invasion. The other is that more effective antibodies which can neutralize the antigens more quickly are produced by somatic hypermutation during the immune response. This phenomenon is named as 'affinity maturation'. ...