The pre-B-cell receptor: selector of fitting immunoglobulin heavy chains for the B-cell repertoire

2005 ◽  
Vol 5 (7) ◽  
pp. 578-584 ◽  
Author(s):  
Fritz Melchers
Keyword(s):  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Cell Repertoire ◽  
Heavy Chains ◽  
B Cell Repertoire

scholarly journals Functionally Convergent B Cell Receptor Sequences in Transgenic Rats Expressing a Human B Cell Repertoire in Response to Tetanus Toxoid and Measles Antigens

2017 ◽  
Vol 8 ◽  
Author(s):  
Jean-Philippe Bürckert ◽  
Axel R. S. X. Dubois ◽  
William J. Faison ◽  
Sophie Farinelle ◽  
Emilie Charpentier ◽  
...  
Keyword(s):  
B Cell ◽  
Tetanus Toxoid ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Transgenic Rats ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Human B Cell

scholarly journals Pre-B Cell Receptor Assesses the Quality of IgH Chains and Tunes the Pre-B Cell Repertoire by Delivering Differential Signals

2006 ◽  
Vol 177 (4) ◽  
pp. 2242-2249 ◽  
Author(s):  
Yohei Kawano ◽  
Soichiro Yoshikawa ◽  
Yoshiyuki Minegishi ◽  
Hajime Karasuyama
Keyword(s):  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Cell Repertoire ◽  
B Cell Repertoire

scholarly journals Memory B cell repertoire for recognition of evolving SARS-CoV-2 spike

2021 ◽  
Author(s):  
Pei Tong ◽  
Avneesh Gautam ◽  
Ian Windsor ◽  
Meghan Travers ◽  
Yuezhou Chen ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Cell Repertoire ◽  
Memory B Cell ◽  
Group Assignment ◽  
Specific Memory ◽  
B Cell Repertoire ◽  
Protective Antibodies

ABSTRACTMemory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.

scholarly journals Transplanted Long-Term Cultured Pre-Bi Cells Expressing Calpastatin Are Resistant to B Cell Receptor–Induced Apoptosis

2001 ◽  
Vol 194 (3) ◽  
pp. 247-254 ◽  
Author(s):  
Antonio Ruiz-Vela ◽  
Fernando Serrano ◽  
Manuel A. González ◽  
José Luis Abad ◽  
Antonio Bernad ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Scid Mice ◽  
Cell Repertoire ◽  
Clonal Deletion ◽  
B Cell Repertoire ◽  
Induced Apoptosis

Long-term cultured pre-B cells are able to differentiate into immunoglobulin (Ig)M-positive B cells (IgM+ cells) when transplanted into severe combined immunodeficient (SCID) mice. Based on previous studies, here we report the development of a reconstitution assay in nonobese diabetic/SCID (NOD/SCID) mice using pre-B cells, which allows us to study the role of calpains (calcium-activated endopeptidases) during B cell development as well as in B cell clonal deletion. Using this model, we show that calpastatin (the natural inhibitor of calpains) inhibits B cell receptor–induced apoptosis in IgM+ cells derived from transplanted mice. We thus hypothesize an important function for calpain in sculpting the B cell repertoire.

scholarly journals A public antibody class recognizes a novel S2 epitope exposed on open conformations of SARS-CoV-2 spike

2021 ◽  
Author(s):  
Mathieu Claireaux ◽  
Tom G Caniels ◽  
Marlon de Gast ◽  
Julianna Han ◽  
Denise Guerra ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Memory B Cells ◽  
B Cell Receptor ◽  
Cell Repertoire ◽  
Fold Enrichment ◽  
B Cell Repertoire ◽  
High Fraction ◽  
Antibody Class

AbstractDelineating the origins and properties of antibodies elicited by SARS-CoV-2 infection and vaccination is critical for understanding their benefits and potential shortcomings. Therefore, we investigated the SARS-CoV-2 spike (S)-reactive B cell repertoire in unexposed individuals by flow cytometry and single-cell sequencing. We found that ∼82% of SARS-CoV-2 S-reactive B cells show a naive phenotype, which represents an unusually high fraction of total human naive B cells (∼0.1%). Approximately 10% of these naive S-reactive B cells shared an IGHV1-69/IGKV3-11 B cell receptor pairing, an enrichment of 18-fold compared to the complete naive repertoire. A proportion of memory B cells, comprising switched (∼0.05%) and unswitched B cells (∼0.04%), was also reactive with S and some of these cells were reactive with ADAMTS13, which is associated with thrombotic thrombocytopenia. Following SARS-CoV-2 infection, we report an average 37-fold enrichment of IGHV1-69/IGKV3-11 B cell receptor pairing in the S-reactive memory B cells compared to the unselected memory repertoire. This class of B cells targets a previously undefined non-neutralizing epitope on the S2 subunit that becomes exposed on S proteins used in approved vaccines when they transition away from the native pre-fusion state because of instability. These findings can help guide the improvement of SARS-CoV-2 vaccines.

scholarly journals Immunoglobulin heavy chains are sufficient to determine most B cell clonal relationships1

2019 ◽  
Author(s):  
Julian Q. Zhou ◽  
Steven H. Kleinstein
Keyword(s):  
B Cell ◽  
High Throughput ◽  
Heavy Chain ◽  
Clonal Expansion ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Light Chains ◽  
Heavy Chains ◽  
Computational Inference ◽  
Cell Clonal Expansion

AbstractB cell clonal expansion is vital for adaptive immunity. High-throughput B cell receptor (BCR) sequencing enables investigating this process, but requires computational inference to identify clonal relationships. This inference usually relies on only the BCR heavy chain, as most current protocols do not preserve heavy:light chain pairing. The extent to which paired light chains aids inference is unknown. Using human single-cell paired BCR datasets, we assessed the ability of heavy chain-based clonal clustering to identify clones. Of the expanded clones identified, <20% grouped cells expressing inconsistent light chains. Heavy chains from these misclustered clones contained more distant junction sequences and shared fewer V segment mutations than the accurate clones. This suggests that additional heavy chain information could be leveraged to refine clonal relationships. Conversely, light chains were insufficient to refine heavy chain-based clonal clusters. Overall, the BCR heavy chain alone is sufficient to identify clonal relationships with confidence.

scholarly journals Deep sequencing of B cell receptor repertoires from COVID-19 patients reveals strong convergent immune signatures

2020 ◽  
Author(s):  
Jacob D. Galson ◽  
Sebastian Schaetzle ◽  
Rachael J. M. Bashford-Rogers ◽  
Matthew I. J. Raybould ◽  
Aleksandr Kovaltsuk ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Deep Sequencing ◽  
Convergent Sequence ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Data Sets ◽  
Heavy Chains ◽  
Patient Responses ◽  
The Uk

AbstractDeep sequencing of B cell receptor (BCR) heavy chains from a cohort of 19 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients and may be a positive indicator of disease outcome. Clonal expansion of the B cell memory response is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 777 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralising antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand and predict positive patient responses.

Rapid, Sustained B Cell Receptor Signaling in Lymphoma B Cells Differs from Normal Signaling in Tumor Infiltrating Nonmalignant B Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 283-283
Author(s):  
Jonathan M. Irish ◽  
Debra K. Czerwinski ◽  
Garry P. Nolan ◽  
Ronald Levy
Keyword(s):  
B Cells ◽  
Cell Signaling ◽  
B Cell ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Life And Death ◽  
Heavy Chains ◽  
Bcr Signaling ◽  
Tumor Biopsies

Abstract The B cell receptor (BCR) drives life and death signaling throughout B cell development, and dysregulation of BCR signaling might be expected to play a role in aberrant proliferation of lymphoma B cells. We have previously used flow cytometry based cell signaling profiles to identify patterns of altered signaling in acute myeloid leukemia that were informative of clinical outcome (Irish et al., Cell, 2004). Here we used a similar signaling profiles approach to compare BCR signaling in normal and lymphoma B cells. However, in addition to comparing follicular lymphoma (FL) B cells with peripheral blood B cells from normal donors, we also interrogated signaling within individual non-tumor B cells infiltrating FL tumor biopsies. By staining for CD20 and BCR light chain isotype (κ vs. λ), we could distinguish tumor and normal B cells within each patient biopsy. Following crosslinking of BCR heavy chains (shared by tumor and non-tumor B cells), we measured phosphorylation of Syk and Btk proteins, as markers of early BCR signaling activity, and Erk1/2 and p38, as markers of downstream BCR signaling effector activity. The BCR signaling network in FL tumor B cells was activated more rapidly than infiltrating non-tumor B cells, achieved greater levels of per-cell signaling, and sustained high levels of signaling over a period of hours. In lymphoma B cells, BCR-mediated Btk and Erk1/2 phosphorylation could reach the normal maximum in as little as 4 minutes, which was much more rapid than the 30–60 minutes required for peak signaling in non-tumor B cells. Strikingly, the timing and magnitude of BCR pathway protein phosphorylation we measured in non-tumor B cells within tumor biopsies was the same as that of normal, mature B cells from peripheral blood. These results suggest that the altered BCR signaling we identified in lymphoma is cell-intrinsic and associated with lymphomagenesis, as opposed to being a general change in tumor microenviornment affecting all B cells within a biopsy. FL tumor B cells from different patients were distinguished by the degree and number of changes to BCR signaling, such that variable profiles of lymphoma signaling kinetics distinguished each patient from the consistent signaling of normal B cells. These results identify cell-intrinsic changes to BCR signaling that may contribute to immortalization of lymphoma B cells and suggest that single cell profiles could identify lymphoma specific BCR-mediated signaling responsible for clinical outcomes.

scholarly journals Inferring processes underlying B-cell repertoire diversity

2015 ◽  
Vol 370 (1676) ◽  
pp. 20140243 ◽  
Author(s):  
Yuval Elhanati ◽  
Zachary Sethna ◽  
Quentin Marcou ◽  
Curtis G. Callan ◽  
Thierry Mora ◽  
...  
Keyword(s):  
B Cell ◽  
Somatic Hypermutation ◽  
Cell Receptor ◽  
Statistical Properties ◽  
Cell Repertoire ◽  
Vdj Recombination ◽  
Site Model ◽  
Human B Cells ◽  
B Cell Repertoire ◽  
Repertoire Diversity

We quantify the VDJ recombination and somatic hypermutation processes in human B cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its initial generation via VDJ recombination and then after selection for functionality. We also infer statistical properties of the somatic hypermutation machinery (exclusive of subsequent effects of selection). Our main results are the following: the B-cell repertoire is substantially more diverse than T-cell repertoires, owing to longer junctional insertions; sequences that pass initial selection are distinguished by having a higher probability of being generated in a VDJ recombination event; somatic hypermutations have a non-uniform distribution along the V gene that is well explained by an independent site model for the sequence context around the hypermutation site.

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