scholarly journals High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes

Science ◽  
2018 ◽  
Vol 362 (6420) ◽  
pp. 1306-1309 ◽  
Author(s):  
Derek Croote ◽  
Spyros Darmanis ◽  
Kari C. Nadeau ◽  
Stephen R. Quake
Keyword(s):  
B Cell ◽  
Immunoglobulin E ◽  
Variable Region ◽  
Cross Reactivity ◽  
Food Allergies ◽  
Ige Antibodies ◽  
High Affinity ◽  
Helminth Infections ◽  
Life Threatening ◽  
Antibody Class

Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.

scholarly journals Human IgE producing B cells have a unique transcriptional program and generate high affinity, allergen-specific antibodies

2018 ◽  
Author(s):  
Derek Croote ◽  
Spyros Darmanis ◽  
Kari C. Nadeau ◽  
Stephen R. Quake
Keyword(s):  
B Cells ◽  
B Cell ◽  
Single Cell ◽  
Recombinant Expression ◽  
Single Cells ◽  
Food Allergies ◽  
Model Organisms ◽  
Biallelic Expression ◽  
Ige Antibodies ◽  
Helminth Infections

AbstractIgE antibodies provide defense against helminth infections, but can also cause life-threatening allergic reactions. Despite their importance to human health, these antibodies and the cells that produce them remain enigmatic due to their scarcity in humans; much of our knowledge of their properties is derived from model organisms. Here we describe the isolation of IgE producing B cells from the blood of individuals with food allergies, followed by a detailed study of their properties by single cell RNA sequencing (scRNA-seq). We discovered that IgE B cells are deficient in membrane immunoglobulin expression and that the IgE plasmablast state is more immature than that of other antibody producing cells. Through recombinant expression of monoclonal antibodies derived from single cells, we identified IgE antibodies which had unexpected cross-reactive specificity for major peanut allergens Ara h 2 and Ara h 3; not only are these among the highest affinity native human antibodies discovered to date, they represent a surprising example of convergent evolution in unrelated individuals who independently evolved nearly identical antibodies. Finally, we discovered that splicing within B cells of all isotypes reveals polarized germline transcription of the IgE, but not IgG4, isotype as well as several examples of biallelic expression of germline transcripts. Our results offer insights into IgE B cell transcriptomics, clonality and regulation, provide a striking example of adaptive immune convergence, and offer an approach for accelerating mechanistic disease understanding by characterizing a rare B cell population underlying IgE-mediated disease at single cell resolution.

scholarly journals Identification of B Cell Epitopes of Blo t 13 Allergen and Cross-Reactivity with Human Adipocytes and Heart Fatty Acid Binding Proteins

2019 ◽  
Vol 20 (24) ◽  
pp. 6107 ◽  
Author(s):  
Marlon Múnera ◽  
Dalgys Martínez ◽  
Alexis Labrada ◽  
Luis Caraballo ◽  
Leonardo Puerta
Keyword(s):  
Fatty Acid ◽  
B Cell ◽  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Cross Reactivity ◽  
Fatty Acid Binding Proteins ◽  
Serum Samples ◽  
Fatty Acid Binding ◽  
B Cell Epitopes ◽  
Human Sera

Cross-reactivity between allergens and human proteins could have a clinical impact in allergic diseases. Blo t 13 is an allergen from the mite Blomia tropicalis, which belongs to the fatty acid binding protein (FABP) family and has structural homology with human FABPs. This work aimed to map B cell epitopes on Blo t 13 and to identify epitopes involved in cross-reactivity with human heart FABP (FABP3) and adipocyte FABP (FABP4). Sera from 25 patients with house dust mite (HDM) allergy that were sensitized to Blo t 13 were used for testing the reactivity of immunoglobulin E (IgE) and IgG to FABP. The epitope mapping of Blo t 13 was performed using overlapping peptides, and cross-reactivity between Blo t 13 and human FABP was analyzed using human sera and anti-Blo t 13 monoclonal antibodies. IgE antibodies to all FABPs were detected in 14/25 serum samples, and IgG was detected in 25/25 serum samples. The cross-reactivity of Blo t 13 was 42% with FABP3 and 48% with FABP4. Two IgE-binding regions were identified in Blo t 13; one between residues 54 and 72 (the main cross-reacting region) and another between residues 111 to 129. Our results suggest that exposure to the Blo t 13 allergen could induce an auto-reactive response to endogenous FABP in allergic patients sensitized to Blo t 13.

scholarly journals The monoclonal anti-phosphorylcholine antibody response in several murine strains: genetic implications of a diverse repertoire.

1977 ◽  
Vol 145 (4) ◽  
pp. 876-891 ◽  
Author(s):  
P J Gearhart ◽  
N H Sigal ◽  
N R Klinman
Keyword(s):  
Monoclonal Antibodies ◽  
Antibody Response ◽  
B Cell ◽  
Variable Region ◽  
Cross Reactivity ◽  
Antibody Specificity ◽  
Cell Repertoire ◽  
Remarkable Similarity ◽  
B Cell Repertoire ◽  
Structural Relationships

The idiotypic identification of monoclonal antibodies has been used to define and enumerate clonotypes within the murine repertoire of B cells specific for phosphorylcholine (PC). The response in the BALB/c strain is dominated by a single antibody specificity which is identical to TEPC 15 protein; however, antibody without the TEPC 15 idiotype appears heterogeneous by idiotypic cross-reactivity and hapten inhibition of binding to antigen. Dissection of the PC-specific repertoire in the AKR, A/He, and C3H strains has indicated that some monoclonal antibodies share binding-site idiotypic determinants with TEPC 15, although these clones represent a minority of the precursor cells. In addition to providing insights into the heterogeneity and expression of the murine B-cell repertoire, these studies emphasize structural relationships between PC-specific clonotypes. Within the BALB/c strain, some antibodies share combining-site-related idiotypic specificities with TEPC 15, but differ in other variable region determinants. Among allotypically distinct strains, there exists a remarkable similarity of variable region determinants in at least a minority of antibodies.

scholarly journals Pomalidomide desensitization in a patient hypersensitive to immunomodulating agents

2017 ◽  
Vol 24 (4) ◽  
pp. 328 ◽  
Author(s):  
J.T Seki ◽  
N. Sakurai ◽  
W. Lam ◽  
D.E. Reece
Keyword(s):  
Immunoglobulin E ◽  
Proteasome Inhibitors ◽  
Preventive Measure ◽  
Cross Reactivity ◽  
Smooth Transition ◽  
Cutaneous Toxicity ◽  
Generation Agent ◽  
Number Of Patients ◽  
Life Threatening ◽  
Grade 3

Despite progressive treatments with tandem stem-cell transplantation, patients with incurable myeloma eventually succumb to relapsed or refractory disease if left untreated. Promising agents such as proteasome inhibitors and immunomodulating imide drugs (imids), including the newer-generation agent pomalidomide, in combination with lower-dose dexamethasone, have been shown to be effective and to significantly improve and prolong survival in pretreated patients.Although the incidence of pomalidomide hypersensitivity reaction (hsr) in this class of drugs is not as well known, we have documented cutaneous toxicity (grade 3 by the Common Terminology Criteria for Adverse Events, version 4) in 2 separate cases (not yet published). Because the imids are chemically, structurally, and pharmacologically similar, it is not unreasonable to consider possible cross-reactivity in pomalidomide recipients who developed hsr when receiving previous lines of imids. As a patient’s advocate, it is only prudent to provide a responsible, and yet practical, means to better address cross-sensitivity for patients.Intervention with the use of a rapid desensitization program (rdp) as a preventive measure should be introduced before initiating pomalidomide. Such a proactive measure for the patient’s safety will ensure a smooth transition into pomalidomide treatment. A hsr can be either related or non-related to immunoglobulin E. As imids become an essential treatment backbone for myeloma and other plasma-cell diseases, an increasing number of patients could experience skin and other life-threatening toxicities, resulting in unnecessary discontinuation of these life-prolonging agents. An extemporaneously prepared pomalidomide suspension developed at our centre enables patients to undergo rdp safely. Patients enjoy a good quality of life and clinical response after the rdp procedure.

scholarly journals A Computational Study of B-Cell Epitopes of Macadamia (Macadamia Integrifolia) Allergens and Identification of its IgE Binding Residues

2021 ◽  
Author(s):  
Shivani Verma
Keyword(s):  
B Cell ◽  
Immunoglobulin E ◽  
Computational Study ◽  
Homology Modelling ◽  
Cross Reactivity ◽  
Computational Tools ◽  
B Cell Epitopes ◽  
Macadamia Integrifolia ◽  
Binding Residues ◽  
Structure Of Proteins

Abstract In contemporary research, biological computational tools have emerged to play a pivotal role in facilitating both cost and time-efficient research. One such domain is addressing the prevailing food allergy issues, where these computational tools have been proven of vital importance. The present study is done as part of an internship at Jozbiz technologies. In the present study, we discuss the identification of IgE(Immunoglobulin E) binding allergy-causing B-Cell epitopes of macadamia (Macadamia integrifolia) allergens, namely AMP23_MACIN, AMP1_MACIN, AMP21_MACIN, MATK_MACIN and 11S1_MACIN. Using seven web servers (ABCPred, ElliPro, BepiPred 1.0b, BcePred, BCPred, CBTOPE and Disco Tope 2.0) twenty-one epitopes and seventeen conformational epitopes were predicted in the present study. The predicted epitopes are analysed in terms of residues having hydrophilicity, polar nature and having exposed surfaces. The unavailable 3-d structure of proteins was developed by homology modelling. Cross-reactivity of Macadamia integrifolia with other food items has also been listed.

Clustering of extensive somatic mutations in the variable region of an immunoglobulin heavy chain gene from a human B cell lymphoma

Cell ◽  
1986 ◽  
Vol 44 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Michael L. Cleary ◽  
Timothy C. Meeker ◽  
Shoshana Levy ◽  
Elizabeth Lee ◽  
Martha Trela ◽  
...  
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Somatic Mutations ◽  
Cell Lymphoma ◽  
Variable Region ◽  
B Cell Lymphoma ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Immunoglobulin Heavy Chain Gene ◽  
Human B Cell
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