scholarly journals Synthetic Standards Combined With Error and Bias Correction Improve the Accuracy and Quantitative Resolution of Antibody Repertoire Sequencing in Human Naïve and Memory B Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Simon Friedensohn ◽  
John M. Lindner ◽  
Vanessa Cornacchione ◽  
Mariavittoria Iazeolla ◽  
Enkelejda Miho ◽  
...  
Keyword(s):  
B Cells ◽  
Bias Correction ◽  
Memory B Cells ◽  
Antibody Repertoire ◽  
Repertoire Sequencing

scholarly journals Accurate Immune Repertoire Sequencing Reveals Malaria Infection Driven Antibody Lineage Diversification in Young Children

2017 ◽  
Author(s):  
Ben S. Wendel ◽  
Chenfeng He ◽  
Mingjuan Qu ◽  
Di Wu ◽  
Stefany M. Hernandez ◽  
...  
Keyword(s):  
B Cells ◽  
Somatic Hypermutation ◽  
Antibody Repertoire ◽  
Infants And Toddlers ◽  
High Coverage ◽  
Sequence Composition ◽  
Age Related ◽  
Sequencing Method ◽  
Repertoire Sequencing ◽  
Lineage Diversification

ABSTRACTAccurately measuring antibody repertoire sequence composition in a small amount of blood is challenging yet important to the understanding of the repertoire response to infections and vaccinations. Here, we describe an accurate and high-coverage repertoire sequencing method, MIDCIRS, which uses as few as 1,000 naïve B cells. Using it, we studied age-related antibody repertoire development and diversification before and during acute malaria in infants (< 12 months old) and toddlers (12 – 47 months old) with 4-8 ml of blood draws. Unexpectedly, we discovered high levels of somatic hypermutation (SHM) in infants as young as three months old. Antibody clonal lineage analysis revealed that both infants and toddlers increase SHM levels upon infection and memory B cells isolated from pre-malaria samples in malaria-experienced individuals continue to induce SHMs upon malaria rechallenge. These results highlight the vast potential of antibody repertoire diversification in infants and toddlers that has not been realized previously.

scholarly journals The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs

Blood ◽  
2014 ◽  
Vol 124 (23) ◽  
pp. 3469-3479 ◽  
Author(s):  
Monica Schaller ◽  
Monique Vogel ◽  
Karim Kentouche ◽  
Bernhard Lämmle ◽  
Johanna A. Kremer Hovinga
Keyword(s):  
B Cells ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Memory B Cells ◽  
Autoimmune Response ◽  
Antibody Repertoire ◽  
Antigen Binding ◽  
Thrombocytopenic Purpura ◽  
Specific Memory ◽  
Key Points

Key Points The spleen harbors ADAMTS13-specific memory B cells following acute acquired TTP. The splenic anti-ADAMTS13 antibody repertoire is characterized by a set of unique and novel CDR3 motifs, 4 shared by 2 patients.

scholarly journals Somatic Hypermutation Shapes the Antibody Repertoire of Memory B Cells in Humans

2001 ◽  
Vol 194 (3) ◽  
pp. 375-378 ◽  
Author(s):  
Eric Meffre ◽  
Nadia Catalan ◽  
Françoise Seltz ◽  
Alain Fischer ◽  
Michel C. Nussenzweig ◽  
...  
Keyword(s):  
B Cells ◽  
Significant Contribution ◽  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Affinity Maturation ◽  
Memory B Cells ◽  
Antibody Repertoire ◽  
Lambda Light Chain ◽  
High Affinity ◽  
Activation Induced Cytidine Deaminase

High-affinity antibodies produced by memory B cells differ from antibodies produced in naive B cells in two respects. First, many of these antibodies show somatic hypermutation, and second, the repertoire of antibodies expressed in memory responses is highly selected. To determine whether somatic hypermutation is responsible for the shift in the antibody repertoire during affinity maturation, we analyzed the immunoglobulin lambda light chain (Igλ) repertoire expressed by naive and antigen-selected memory B cells in humans. We found that the Igλ repertoire differs between naive and memory B cells and that this shift in the repertoire does not occur in the absence of somatic hypermutation in patients lacking activation-induced cytidine deaminase (AID). Our work suggests that somatic hypermutation makes a significant contribution to shaping the antigen-selected antibody repertoire in humans.

scholarly journals Natural occurrence and origin of somatically mutated memory B cells in mice.

1992 ◽  
Vol 176 (2) ◽  
pp. 427-438 ◽  
Author(s):  
B Schittek ◽  
K Rajewsky
Keyword(s):  
B Cells ◽  
B Cell ◽  
Immunoglobulin G ◽  
Memory B Cells ◽  
Antibody Repertoire ◽  
Natural Occurrence ◽  
Cell Pool ◽  
Vh Genes ◽  
Environmental Antigens ◽  
Delta Cells

While most murine peripheral B cells express germline-encoded antibodies of classes M and D (mu+ delta+ cells), small numbers of memory B cells expressing somatically mutated immunoglobulin G antibodies are generated upon T cell-dependent immunization. Analyzing the antibody repertoire of the mu-delta- B cell pool in unimmunized mice, we show that these cells express somatically mutated VH genes and that most of these genes derive from a set of germline VH genes dominantly expressed by mu+delta+ B cells. Thus, class-switched memory B cells are generated in the absence of intentional immunization, presumably in response to environmental antigens. These cells are either recruited from mu+delta+ B cells or selected from newly arising B cells in parallel to the latter, by the same antigens.

scholarly journals Proteo-Genomic Analysis Identifies Two Major Sites of Vulnerability on Ebolavirus Glycoprotein for Neutralizing Antibodies in Convalescent Human Plasma

2021 ◽  
Vol 12 ◽  
Author(s):  
Pavlo Gilchuk ◽  
Adrian Guthals ◽  
Stefano R. Bonissone ◽  
Jared B. Shaw ◽  
Philipp A. Ilinykh ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Ebola Virus ◽  
Single Cells ◽  
Humoral Response ◽  
Memory B Cells ◽  
The Body ◽  
Antibody Repertoire ◽  
Antigenic Sites ◽  
Cell Antibody

Three clinically relevant ebolaviruses – Ebola (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) viruses, are responsible for severe disease and occasional deadly outbreaks in Africa. The largest Ebola virus disease (EVD) epidemic to date in 2013-2016 in West Africa highlighted the urgent need for countermeasures, leading to the development and FDA approval of the Ebola virus vaccine rVSV-ZEBOV (Ervebo®) in 2020 and two monoclonal antibody (mAb)-based therapeutics (Inmazeb® [atoltivimab, maftivimab, and odesivimab-ebgn] and Ebanga® (ansuvimab-zykl) in 2020. The humoral response plays an indispensable role in ebolavirus immunity, based on studies of mAbs isolated from the antibody genes in peripheral blood circulating ebolavirus-specific human memory B cells. However, antibodies in the body are not secreted by circulating memory B cells in the blood but rather principally by plasma cells in the bone marrow. Little is known about the protective polyclonal antibody responses in convalescent plasma. Here we exploited both single-cell antibody gene sequencing and proteomic sequencing approaches to assess the composition of the ebolavirus glycoprotein (GP)-reactive antibody repertoire in the plasma of an EVD survivor. We first identified 1,512 GP-specific mAb variable gene sequences from single cells in the memory B cell compartment. Using mass spectrometric analysis of the corresponding GP-specific plasma IgG, we found that only a portion of the large B cell antibody repertoire was represented in the plasma. Molecular and functional analysis of proteomics-identified mAbs revealed recognition of epitopes in three major antigenic sites - the GP head domain, the glycan cap, and the base region, with a high prevalence of neutralizing and protective mAb specificities that targeted the base and glycan cap regions on the GP. Polyclonal plasma antibodies from the survivor reacted broadly to EBOV, BDBV, and SUDV GP, while reactivity of the potently neutralizing mAbs we identified was limited mostly to the homologous EBOV GP. Together these results reveal a restricted diversity of neutralizing humoral response in which mAbs targeting two antigenic sites on GP – glycan cap and base – play a principal role in plasma-antibody-mediated protective immunity against EVD.

Sign in / Sign up

Export Citation Format

Share Document