Similarity and divergence in the development and expression of the mouse and human antibody repertoires

2006 ◽  
Vol 30 (1-2) ◽  
pp. 119-135 ◽  
Author(s):  
Harry W. Schroeder
Keyword(s):  
Human Antibody ◽  
Antibody Repertoires

Production of human antibody repertoires in transgenic mice

1997 ◽  
Vol 8 (4) ◽  
pp. 455-458 ◽  
Author(s):  
Marianne Brüggemann ◽  
Michael J Taussig
Keyword(s):  
Transgenic Mice ◽  
Human Antibody ◽  
Antibody Repertoires

scholarly journals Signatures of selection in the human antibody repertoire: Selective sweeps, competing subclones, and neutral drift

2019 ◽  
Vol 116 (4) ◽  
pp. 1261-1266 ◽  
Author(s):  
Felix Horns ◽  
Christopher Vollmers ◽  
Cornelia L. Dekker ◽  
Stephen R. Quake
Keyword(s):  
B Cell ◽  
Binding Affinity ◽  
Antibody Repertoire ◽  
Human Antibody ◽  
Selective Sweeps ◽  
Human Immune System ◽  
Evolutionary Processes ◽  
Neutral Drift ◽  
Cell Lineages ◽  
Antibody Repertoires

Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the population genetic signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically. We measured the dynamics and genetic diversity of B cell responses in five adults longitudinally before and after influenza vaccination using high-throughput antibody repertoire sequencing. We identified vaccine-responsive B cell lineages that carry signatures of selective sweeps driven by positive selection, and discovered that they often display evidence for selective sweeps favoring multiple subclones. We also found persistent B cell lineages that exhibit stable population dynamics and carry signatures of neutral drift. By exploiting the relationship between B cell fitness and antibody binding affinity, we demonstrate the potential for using phylogenetic approaches to identify antibodies with high binding affinity. This quantitative characterization reveals that antibody repertoires are shaped by an unexpectedly broad spectrum of evolutionary processes and shows how signatures of evolutionary history can be harnessed for antibody discovery and engineering.

Characteristics of human antibody repertoires following active immune responses in vivo

1996 ◽  
Vol 33 (7-8) ◽  
pp. 583-592 ◽  
Author(s):  
Mats Ohlin ◽  
Carl A.K. Borrebaeck
Keyword(s):  
Immune Responses ◽  
Human Antibody ◽  
Antibody Repertoires

scholarly journals Regulatory Approved Monoclonal Antibodies Contain Framework Mutations Predicted From Human Antibody Repertoires

2021 ◽  
Vol 12 ◽  
Author(s):  
Brian M. Petersen ◽  
Sophia A. Ulmer ◽  
Emily R. Rhodes ◽  
Matias F. Gutierrez-Gonzalez ◽  
Brandon J. Dekosky ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
High Frequency ◽  
In Silico ◽  
Sequence Data ◽  
Antibody Repertoire ◽  
Human Antibody ◽  
Therapeutic Antibodies ◽  
T Cell Epitopes ◽  
Antibody Repertoires ◽  
Dynamics Simulations

Monoclonal antibodies (mAbs) are an important class of therapeutics used to treat cancer, inflammation, and infectious diseases. Identifying highly developable mAb sequences in silico could greatly reduce the time and cost required for therapeutic mAb development. Here, we present position-specific scoring matrices (PSSMs) for antibody framework mutations developed using baseline human antibody repertoire sequences. Our analysis shows that human antibody repertoire-based PSSMs are consistent across individuals and demonstrate high correlations between related germlines. We show that mutations in existing therapeutic antibodies can be accurately predicted solely from baseline human antibody sequence data. We find that mAbs developed using humanized mice had more human-like FR mutations than mAbs originally developed by hybridoma technology. A quantitative assessment of entire framework regions of therapeutic antibodies revealed that there may be potential for improving the properties of existing therapeutic antibodies by incorporating additional mutations of high frequency in baseline human antibody repertoires. In addition, high frequency mutations in baseline human antibody repertoires were predicted in silico to reduce immunogenicity in therapeutic mAbs due to the removal of T cell epitopes. Several therapeutic mAbs were identified to have common, universally high-scoring framework mutations, and molecular dynamics simulations revealed the mechanistic basis for the evolutionary selection of these mutations. Our results suggest that baseline human antibody repertoires may be useful as predictive tools to guide mAb development in the future.

scholarly journals Decrease of Clone Diversity in IgM Repertoires of HBV Chronically Infected Individuals With High Level of Viral Replication

2021 ◽  
Vol 11 ◽  
Author(s):  
Binbin Hong ◽  
Lizhi Wang ◽  
Chunlan Huang ◽  
Xiaoju Hong ◽  
Alan Liu ◽  
...  
Keyword(s):  
Viral Replication ◽  
Healthy Adults ◽  
Human Antibody ◽  
Low Level ◽  
Hbv Replication ◽  
Cdr3 Length ◽  
Chronic Hbv ◽  
Antibody Repertoires ◽  
High Level ◽  
The Comparative Study

High-throughput antibody sequencing allows in-depth insights into human antibody repertoires. To investigate the characteristics of antibody repertoires in patients with chronic HBV infection, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of B lymphocytes from healthy adults and the HBV carriers with high or low level of viral replication. The comparative study revealed high levels of similarity between the IgM and IgG repertoires of the HBV carriers and the healthy adults, including the somatic mutations in V regions, the average CDR3 length, and the occurrence of junctional modifications. Nevertheless, the diversity of the unique clones decreased and some clusters of unique clones expanded in the IgM repertoire of chronic HBV carriers (CHB) compared with healthy adults (HH) and inactive HBV carriers (IHB). Such difference in clone diversity and expansion was not observed in the IgG repertoires of the three populations. More shared antibody clones were found between the IgM repertoires of IHB and HH than that found between CHB and HH (7079 clones vs. 2304 clones). Besides, the biased used IGHD genes were IGHD2-2 and IGHD3-3 in CHB library but were IGHD3-10 and IGHD3-22 in IHB and HH library. In contrast, for IgG repertories, the preferred used VDJ genes were similar in all the three populations. These results indicated that low level of serum HBV might not induce significant changes in BCR repertoires, and high level of HBV replication could have more impacts on IgM repertories than IgG repertoires. Taken together, our findings provide a better understanding of the antibody repertoires of HBV chronically infected individuals.

Full-scale ‘naïve’ human antibody repertoires assembled from VH and VL variable regions

1997 ◽  
Vol 8 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Régis Sodoyer ◽  
Isabelle Peubez ◽  
Corinne Pion ◽  
Joseline Dubayle ◽  
Paul Jacquemot ◽  
...  
Keyword(s):  
Full Scale ◽  
Human Antibody ◽  
Variable Regions ◽  
Antibody Repertoires

scholarly journals Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing

10.3791/58804 ◽  
2019 ◽  
Author(s):  
Lin Sun ◽  
Naoko Kono ◽  
Hiroyuki Toh ◽  
Hanbing Xue ◽  
Kaori Sano ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Human Antibody ◽  
Next Generation ◽  
Antibody Repertoires ◽  
Generation Sequencing

scholarly journals Distinct antibody repertoires against endemic human coronaviruses in children and adults

2020 ◽  
Author(s):  
Taushif Khan ◽  
Mahbuba Rahman ◽  
Fatima Al Ali ◽  
Susie S. Y. Huang ◽  
Manar Ata ◽  
...  
Keyword(s):  
B Cell ◽  
Antibody Responses ◽  
Human Antibody ◽  
Cell Responses ◽  
Coronavirus Infection ◽  
Antibody Repertoires ◽  
Human Coronaviruses ◽  
Antibody Specificities ◽  
Species Specific ◽  
Therapeutic Monoclonal Antibodies

AbstractFour endemic human coronaviruses (HCoVs) are commonly associated with acute respiratory infection in humans. B cell responses to these “common cold” viruses remain incompletely understood. Here we report a comprehensive analysis of CoV-specific antibody repertoires in 231 children and 1168 adults using phage-immunoprecipitation sequencing. Seroprevalence of antibodies to endemic HCoVs ranged between ~4 and 27% depending on the species and cohort. We identified at least 136 novel linear B cell epitopes. Antibody repertoires against endemic HCoVs were qualitatively different between children and adults in that anti-HCoV IgG specificities more frequently found among children targeted functionally important and structurally conserved regions of the spike, nucleocapsid and matrix proteins. Moreover, antibody specificities targeting the highly conserved fusion peptide region and S2’ cleavage site of the spike protein were broadly cross-reactive with peptides of epidemic human and non-human coronaviruses. In contrast, an acidic tandem repeat in the N-terminal region of the Nsp3 subdomain of the HCoV-HKU1 polyprotein was the predominant target of antibody responses in adult donors. Our findings shed light on the dominant species-specific and pan-CoV target sites of human antibody responses to coronavirus infection, thereby providing important insights for the development of prophylactic or therapeutic monoclonal antibodies and vaccine design.

Human Antibody Repertoires

2008 ◽  
pp. 261-277 ◽  
Author(s):  
Per-Johan Meijer ◽  
Lars S. Nielsen ◽  
Johan Lantto ◽  
Allan Jensen
Keyword(s):  
Human Antibody ◽  
Antibody Repertoires

scholarly journals Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

2016 ◽  
Vol 113 (19) ◽  
pp. E2636-E2645 ◽  
Author(s):  
Brandon J. DeKosky ◽  
Oana I. Lungu ◽  
Daechan Park ◽  
Erik L. Johnson ◽  
Wissam Charab ◽  
...  
Keyword(s):  
B Cells ◽  
Light Chain ◽  
Solvent Accessible Surface Area ◽  
Antibody Repertoire ◽  
Human Antibody ◽  
Variable Regions ◽  
Cell Immunity ◽  
Depth Analysis ◽  
Antibody Repertoires ◽  
Complementarity Determining Region

Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19+CD20+CD27− IgM-naive B cells, >120,000 antibody clusters from CD19+CD20+CD27+ antigen–experienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ–Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease.

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