Antibody-encoding repertoires of bone marrow and peripheral blood—a focus on IgE

Levin, Mattias; Levander, Fredrik; Pálmason, Róbert; Greiff, Lennart; Ohlin, Mats

doi:10.1016/j.jaci.2016.06.040

Cited by 34 publications

(47 citation statements)

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“…IgM heavy chain variable domain-encoding gene repertoires were isolated by RT-PCR from transcriptomes of PB and BM collected out of season of most seasonal allergens from six allergic subjects [3]. Ethical approval and informed consent had been obtained from all donors.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

“…Ethical approval and informed consent had been obtained from all donors. Sequencing was performed using the 2 × 300 bp MiSeq technology (Illumina, Inc., San Diego, CA, USA) at the National Genomics Infrastructure (SciLifeLab, Stockholm, Sweden) [3]. Details of sequence output and availability are outlined in Table 1.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

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Data on haplotype-supported immunoglobulin germline gene inference

et al. 2017

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Data that defines IGHV (immunoglobulin heavy chain variable) germline gene inference using sequences of IgM-encoding transcriptomes obtained by Illumina MiSeq sequencing technology are described. Such inference is used to establish personalized germline gene sets for in-depth antibody repertoire studies and to detect new antibody germline genes from widely available immunoglobulin-encoding transcriptome data sets. Specifically, the data has been used to validate (Parallel antibody germline gene and haplotype analyses support the validity of immunoglobulin germline gene inference and discovery (DOI: 10.1016/j.molimm.2017.03.012) (Kirik et al., 2017) [1]) the inference process. This was accomplished based on analysis of the inferred germline genes’ association to the donors’ different haplotypes as defined by their different, expressed IGHJ alleles and/or IGHD genes/alleles. The data is important for development of validated germline gene databases containing entries inferred from immunoglobulin-encoding transcriptome sequencing data sets, and for generation of valid, personalized antibody germline gene repertoires.

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Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Data on haplotype-supported immunoglobulin germline gene inference

et al. 2017

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“…To detect clonally‐expanded populations stimulated by vaccination or infection, most often, researchers have used other cellular phenotypic surrogates, for example, by isolating B cells in the blood that have adopted a plasmablast phenotype, or one of the other activated B cell phenotypes that have been recently described such as CD71 + activated B cells (ABCs) or CD21low B cells . The advent of HTS methods for sequencing the BCRs or TCRs of thousands to millions of individual B cells and T cells from bulk populations has also made it possible to directly detect the clonally‐expanded fraction of the repertoire in human blood or tissue samples . Indeed, initial studies using HTS to detect clonally‐expanded B cells following influenza vaccination, and comparing these to the clones identified in flow‐sorted plasmablasts from the same subjects, indicated that not all of the expanded clones could be attributed to plasmablasts; subsequent studies identified a novel CD71 + non‐plasmablast population of ABCs as a separate phenotypic subset with only partial clonal overlap with plasmablasts, accounting for many of the ‘missing’ clones .…”

Section: Tracking Clonal Responses To Vaccination and Infectionmentioning

confidence: 99%

“…Patients undergoing immunotherapy show stimulation of increased levels of the allergen‐specific B cells in the blood, but the specific correlates of desensitization following immunotherapy are still under investigation. Other interesting work in this area has explored the frequency of IgE‐expressing B‐lineage clones, likely representing plasma cells or plasmacytoid B cell phenotypes, in other tissue sites, including the bone marrow, which contains abundant IgE+ plasma cells . Longitudinal studies of aeroallergen‐allergic patient blood and nasal biopsies indicate that allergen‐specific IgE‐containing clones can be long‐lived in the body (persisting for over 1 year).…”

Section: Repertoires In Pathologic Conditionsmentioning

confidence: 99%

Human adaptive immune receptor repertoire analysis—Past, present, and future

Nielsen

Boyd

2018

Immunological Reviews

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The genes encoding adaptive immune antigen receptors, namely the immunoglobulins expressed in membrane-bound or secreted forms by B cells, and the cell surface T cell receptors, are unique in human biology because they are generated by combinatorial rearrangement of the genomic DNA. The diversity of receptors so generated in populations of lymphocytes enables the human immune system to recognize antigens expressed by pathogens, but also underlies the pathological specificity of autoimmune diseases and the mistargeted immunity in allergies. Several recent technological developments, foremost among them the invention of high-throughput DNA sequencing instruments, have enabled much deeper and thorough evaluation of clones of human B cells and T cells and the antigen receptors they express during physiological and pathogenic immune responses. The evolutionary struggles between host adaptive immune responses and populations of pathogens are now open to greater scrutiny, elucidation of the underlying reasons for successful or failed immunity, and potential predictive modeling, than ever before. Here we give an overview of the foundations, recent progress, and future prospects in this dynamic area of research.

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“…Within immunoglobulins, there are key differences found between subclasses. Recently, both IgE and IgG4 were shown to contain significantly more variable domain glycans than other isotypes (46,54,58). In particular, bone marrow-derived IgE was found to contain twice as many variable domain glycans as other immunoglobulin subclasses in healthy donors (46), despite the fact that they often carried fewer mutations.…”

Section: Subclass-specific Differencesmentioning

confidence: 99%

A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma

et al. 2020

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N-linked glycans play an important role in immunity. Although the role of N-linked glycans in the Fragment crystallizable (Fc) region of immunoglobulins has been thoroughly described, the function of N-linked glycans present in Ig-variable domains is only just being appreciated. Most of the N-linked glycans harbored by immunoglobulin variable domain are of the complex biantennary type and are found as a result of the presence of N-linked glycosylation that most often have been introduced by somatic hypermutation. Furthermore, these glycans are ubiquitously present on autoantibodies observed in some autoimmune diseases as well as certain B-cell lymphomas. For example, variable domain glycans are abundantly found by anti-citrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA) as well as by the B-cell receptors of follicular lymphoma (FL). In FL, variable domain glycans are postulated to convey a selective advantage through interaction with lectins and/or microbiota, whereas the contribution of variable domain glycans on autoantibodies is not known. To aid the understanding how these seemingly comparable phenomena contribute to a variety of deranged B-responses in such different diseases this study summarizes the characteristics of ACPA and other auto-antibodies with FL and healthy donor immunoglobulins, to identify the commonalities and differences between variable domain glycans in autoimmune and malignant settings. Our finding indicate intriguing differences in variable domain glycan distribution, frequency and glycan composition in different conditions. These findings underline that variable domain glycosylation is a heterogeneous process that may lead to a number of pathogenic outcomes. Based on the current body of knowledge, we postulate three disease groups with distinct variable domain glycosylation patterns, which might correspond with distinct underlying pathogenic processes.

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Antibody-encoding repertoires of bone marrow and peripheral blood—a focus on IgE

Cited by 34 publications

References 10 publications

Data on haplotype-supported immunoglobulin germline gene inference

Data on haplotype-supported immunoglobulin germline gene inference

Human adaptive immune receptor repertoire analysis—Past, present, and future

A Comparison of Immunoglobulin Variable Region N-Linked Glycosylation in Healthy Donors, Autoimmune Disease and Lymphoma

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