Generation of Antibody Diversity

Backhaus, Oliver

doi:10.5772/intechopen.72818

Cited by 5 publications

(5 citation statements)

References 42 publications

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“…This diversity arises due to several factors contributing to the formation of antibodies with distinct specificities within the host. Firstly, the genetic recombination and somatic hypermutation processes during B cell development generate a wide range of antibody sequences, leading to the production of antibodies recognizing diverse antigens [34] . Secondly, exposure to a plethora of antigens throughout an individual's lifetime triggers the activation and clonal expansion of various B cell clones, each producing antibodies targeting specific antigens encountered [35] .…”

Section: Mathematical Simulation Of Virus-host Interactions Consideri...mentioning

confidence: 99%

Dynamic Modeling of Antibody Repertoire Reshaping in Response to Viral Infections

Xu,

Zhang

et al. 2024

Preprint

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For many years, researchers have emphasized the production of high-affinity specific antibodies by hosts during viral infections. However, this has made it challenging for immunologists to systematically evaluate the initiation mechanisms of humoral immunity in specific immune responses. Employing mathematical modeling, we have systematically investigated the dynamic changes of the entire antibody atlas in response to exogenous antigenic stimuli, including viral infections. Our study reveals that the host’s antibody atlas is reshaped during viral infection, not through the proliferation of individual antibody types, but rather through the proliferation of antibody pools with strong binding activity. Moreover, we observe a contraction in pools of antibodies with low binding activity. We have identified the crucial role of self-antigens in maintaining antibody persistence, which can effectively explain the organism’s lifelong protection against pathogens that are less prone to mutation. Using this model, we further explore the mechanisms underlying original antigenic sin and elucidate the specific practical applications of this model. This research transcends the limitations of mere mathematical parameter fitting, as we endeavor to elucidate the complex humoral immune processes using physical mechanisms as a foundation. Our work contributes to a renewed understanding of the antibody elicitation process in specific immune responses.

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Section: Mathematical Simulation Of Virus-host Interactions Consideri...mentioning

confidence: 99%

Dynamic Modeling of Antibody Repertoire Reshaping in Response to Viral Infections

Xu,

Zhang

et al. 2024

Preprint

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“…Gray regions correspond to light-chain segments, which are combined with heavy chains post-translationally. Figure inspiration was drawn from various sources (Little et al, 2015;Feederle and Schepers, 2017;Backhaus, 2018). chromosome 14 possesses roughly 50 functional V segments, 27 functional D segments, and six functional J segments (Rodriguez et al, 2020).…”

Section: Immunoglobulin Gene Loci and V(d)j Recombinationmentioning

confidence: 99%

Section: Antigen Receptor Diversitymentioning

confidence: 99%

May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression

Williams

Sikora

Hammer

et al. 2022

Front. Cell Dev. Biol.

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How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.

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“…Besides different germ line segments, there exist a relative large number of pseudogenes of which some can undergo recombination leading to a nonfunctional variable region. An overview of the number of gene segments in the respective gene locus is given in Table 1 (slightly modified from IMGT [5]).…”

Section: Combinatorial Diversity Of Immunoglobulinsmentioning

confidence: 99%

Generation of Antibody Diversity

2020

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Because of the huge diversity, the immunoglobulin repertoire cannot be encoded by static genes, which would explode the genomic capacity comprising about 20,000-25,000 human genes. The immunoglobulin repertoire is provided by the process of somatic germ line recombination, which is the only controlled alteration of the genomic DNA after meiosis. It takes place in mammalian B lymphocyte (B cells) precursors in the bone marrow. The genome germ line sequence of undeveloped B cells is organized in gene segments and compromise V (variable), D (diversity), and J (joining) gene segments constituting the variable domain of the heavy chain and only V and J genes for building up the variable domain of the light chain. The rearrangement of the variable region follows a strict order. The following processes that participate in the generation of antibody diversity were summarized-allelic, combinational, and junctional diversity, pairing of IgH and IgL, and receptor editing-which all together produce the primary antigen repertoire (pre-antigen stimulation). When a B cell encounters a foreign antigen, affinity maturation and class switch are induced. Thereby the antibody repertoire increases. The resulting secondary immunoglobulin repertoire reveals in humans at least 10 11 specificities for different antigens.

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Generation of Antibody Diversity

Cited by 5 publications

References 42 publications

Dynamic Modeling of Antibody Repertoire Reshaping in Response to Viral Infections

Dynamic Modeling of Antibody Repertoire Reshaping in Response to Viral Infections

May the Odds Be Ever in Your Favor: Non-deterministic Mechanisms Diversifying Cell Surface Molecule Expression

Generation of Antibody Diversity

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