China
Africa
Explore chapters and articles related to this topic
Phylogeny of the mucosal immune system
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Robert D. Miller, Irene Salinas
In birds, B cells that have undergone V(D)J recombination in the bone marrow must migrate to the bursa to complete their development. In the bursa of Fabricius, avian B cells complete their development by introducing mutations into their recombined V genes using AID-mediated gene conversion. This is an essential step because of the lack of repertoire diversity generated by V(D)J recombination alone. The chicken IgH locus contains only a single functional V gene and a large array of nonfunctional V pseudogenes. Although the pseudogenes cannot be recombined and expressed, they can be used as a source of donor sequences for gene conversion (Figure 2.4).
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
B lymphocytes also develop from hematopoietic progenitors in the bone marrow, where they undergo the initial process of differentiation and selection [6]. They are distinguished from T cells and NK cells by the expression of the B cell receptor (BCR) on their plasma membrane. Development of B cells occurs in several stages, marked by various patterns of gene expression, and an arrangement of the immunoglobulin H chain and L chain gene loci. They also undergo the V(D)J recombination of their immunoglobulins. To complete their development, immature B cells migrate from the bone marrow to the spleen. Once fully differentiated, B cells can secrete antibodies and comprise the humoral component of the adaptive immunity. In addition, B cells present antigen and secrete cytokines. The BCR enables each B cell clone to bind a specific antigen and initiate an antibody response. Activation of B cells occurs via antigen recognition by BCRs and requires a secondary activation signal provided either by T helper cells or by the antigen itself.
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
A critical step in T and B lymphopoiesis is the complex process of forming functional, but not autoreactive, antigen-specific T cell (TCR) and B cell (BCR) receptors (Figures 10.5 and 10.6). A diverse array of receptors is generated from the recombination of a limited number of germline gene segments (variable [V], diversity [D], and joining [J]) (Figures 7.1 and 7.2). The initiation V(D)J recombination requires the expression of RAG genes, which are restricted to lymphocyte progenitors and developing lymphocytes. In addition, lineage-specific, cis elements control the accessibility of DNA regions to RAG-1 and RAG-2. This and other control processes ensures that TCR genes are only rearranged to completion in T lymphocytes and BCR genes are only rearranged to completion in B lymphocytes.
Challenges in antibody structure prediction
Published in mAbs, 2023
Monica L. Fernández-Quintero, Janik Kokot, Franz Waibl, Anna-Lena M. Fischer, Patrick K. Quoika, Charlotte M. Deane, Klaus R. Liedl
Predicting the three-dimensional (3D) structure of a protein based solely on the amino-acid sequence is one of the grand challenges in the field of protein structure prediction.1 Accurate prediction of the 3D structure of a protein is critical to understand its function, as the shape of the protein determines its properties and ultimately its function. To determine the state-of-the-art methods in protein structure prediction, the biennial community-based benchmarking experiment “Critical Assessment of methods in protein Structure Prediction (CASP)” was established.2–4 In CASP14 (2020), DeepMind showcased AlphaFold2, a program based on artificial intelligence (AI) that directly processes multiple sequence alignments.5 Comparable accuracies in predicting protein structures can also be achieved with other methods including RoseTTAFold,6 and specialized tools for antibodies which incorporate the recent advances.7–9 Those tools are highly accurate based on global measures, often with root mean square deviations (RMSDs) to the crystal structure of less than 1 Å. However, there are often higher inaccuracies in specific parts of the protein that should be carefully reviewed.10,11 Post-translational modifications are omitted, but can sometimes be added afterwards.12 Furthermore, the accuracy for multimers, such as antibodies, is still lower.13 Additional challenges can arise for antibodies since VDJ recombination events do not follow the classical pathway of evolution.14
Electrostatic Complementarity of T-Cell Receptor-Alpha CDR3 Domains and Mutant Amino Acids Is Associated with Better Survival Rates for Sarcomas
Published in Pediatric Hematology and Oncology, 2021
Michelle Yeagley, Boris I. Chobrutskiy, Etienne C. Gozlan, Nikhila Medikonda, Dhruv N. Patel, Shayan Falasiri, Blake M. Callahan, Taha Huda, George Blanck
Two hundred sixty-two whole exome sequence (WXS) files for TCGA-SARC case IDs representing 261 soft tissue sarcoma (STS) patients were recovered from the genomic data commons (GDC) (https://portal.gdc.cancer.gov/repository) per National Center for Biotechnology Information’s Database of Genotypes and Phenotypes (dbGaP) approved project number 6300. (In one case, there was both a metastatic and primary tumor sample represented by a WXS files, respectively. In all other cases, only a primary tumor sample was used to prepare the WXS files.) Immune receptor V(D)J recombination reads were recovered using previously published and extensively benchmarked processes,19 with read validations based on known V and J sequences obtained from The International Immunogenetics Information System (http://www.imgt.org/). The CDR3 domains of the V(D)J recombination reads were then identified and translated. Both processes were performed using a previously described algorithm,17 and the original script is at github.com (https://github.com/bchobrut-USF/lgg_idh1). The net charge per residue (NCPR) was calculated for each CDR3 using the localCIDER python package (http://pappulab.github.io/localCIDER/).
Current strategies for detecting functional convergence across B-cell receptor repertoires
Published in mAbs, 2021
Matthew I. J. Raybould, Anthony R. Rees, Charlotte M. Deane
There is now a large body of evidence to suggest that certain germline gene segments are used preferentially across individuals during V(D)J recombination. Both Boyd et al. in 201018 and Glanville et al. in 201119 showed that the use frequencies of individual IGHV genes in the naïve antibody repertoire varied between 0.1% and 10%, while IGHD gene usage can vary between 1 and 15%, displaying a strong preference for one of three reading frames.20,21 Similar biases are observed in the usage of the IGHJ and light-chain genes, challenging the notion that “all immunoglobulin genes are made equal”.22 Biases can even be observed during the terminal deoxynucleotidyl transferase-catalyzed non-templated N-additions.23–25 After applying these estimates of the effects of biased gene selections, effective naïve BCR repertoire clonal diversity could be as low as 107, closer to the levels frequently observed.1