Immunoglobulin Analysis Tool: A Novel Tool for the Analysis of Human and Mouse Heavy and Light Chain Transcripts

Rogosch, Tobias; Kerzel, Sebastian; Hoi, Kam Hon; Zhang, Zhixin; Maier, Rolf F.; Ippolito, Gregory C.; Zemlin, Michael

doi:10.3389/fimmu.2012.00176

Cited by 67 publications

(52 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After passing the quality control criteria, sequences were submitted to IGMT/HighV-QUEST database for analysis 67 . The files from IMGT/highV-QUEST were imported into IgAT immunoglobulin analysis tool for further analysis 68 .…”

Section: Methodsmentioning

confidence: 99%

Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells

et al. 2015

View full text Add to dashboard Cite

Random recombination of antibody heavy-and light-chain genes results in a diverse B-cell receptor (BCR) repertoire including self-reactive BCRs. However, tolerance mechanisms that prevent the development of self-reactive B cells remain incompletely understood. The absence of the surrogate light chain, which assembles with antibody heavy chain forming a pre-BCR, leads to production of antinuclear antibodies (ANAs). Here we show that the naive follicular B-cell pool is enriched for cells expressing prototypic ANA heavy chains in these mice in a non-autoimmune background with a broad antibody repertoire. This results in the spontaneous formation of T-cell-dependent germinal centres that are enriched with B cells expressing prototypic ANA heavy chains. However, peripheral tolerance appears maintained by selection thresholds on cells entering the memory B-cell and plasma cell pools, as exemplified by the exclusion of cells expressing the intrinsically self-reactive V H 81X from both pools.

show abstract

Section: Methodsmentioning

confidence: 99%

Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Barcoded sequence data were separated using Geneious software, and IMGT/ HighVQuest was used for alignment to germline IgH VDJ regions. IgAT software was used to generate descriptive statistics and calculate CDR3 characteristics (39). Software provided by Ramit Mehr's laboratory was used for clonal analysis and combination of clones from various samples.…”

Section: Hep-2 Immunofluorescence Assay Testsmentioning

confidence: 99%

CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

Schwartz

Kolhatkar

Thouvenel

et al. 2014

The Journal of Immunology

View full text Add to dashboard Cite

Control of peripheral B cell development and homeostasis depends critically on coordinate signals received through the BAFFRs and BCRs. The extent to which other signals contribute to this process, however, remains undefined. We present data indicating that CD4+ T cells directly influence naive B cell development via CD40 signaling. Loss of CD4+ T cells or CD40–CD40L interaction leads to reduced B cell homeostatic proliferation and hindered B cell reconstitution posttransplantation. Furthermore, we demonstrate that in the absence of CD40 signals, these events are modulated by BCR self-reactivity. Strikingly, murine models lacking CD40 reveal a broadly altered BCR specificity and limited diversity by both single-cell cloning and high-throughput sequencing techniques. Collectively, our results imply that any setting of T cell lymphopenia or reduced CD40 function, including B cell recovery following transplantation, will impact the naive B cell repertoire.

show abstract

“…Somatic mutation rates and Ag selection were studied in the VH genes, using the algorithms of Dahlke et al (44), Lossos et al (45), and Chang and Casali (46), as described previously (47). Sequence analyses were performed using IMGT/V-QUEST (42) and the Ig analysis tool (IgAT) (48). Phylogenetic trees were compiled using ClustalX (49) and Treedyn (50).…”

Section: Sequence Analysismentioning

confidence: 99%

IgG4 and IgE Transcripts in Childhood Allergic Asthma Reflect Divergent Antigen-Driven Selection

Rogosch

Kerzel

Dey

et al. 2014

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The physiologic function of the “odd” Ab IgG4 remains enigmatic. IgG4 mediates immunotolerance, as, for example, during specific immunotherapy of allergies, but it mediates tissue damage in autoimmune pemphigus vulgaris and “IgG4-related disease.” Approximately half of the circulating IgG4 molecules are bispecific owing to their unique ability to exchange half-molecules. Better understanding of the interrelation between IgG4 and IgE repertoires may yield insight into the pathogenesis of allergies and into potential novel therapies that modulate IgG4 responses. We aimed to compare the selective forces that forge the IgG4 and IgE repertoires in allergic asthma. Using an IgG4-specific RT-PCR, we amplified, cloned, and sequenced IgG4 H chain transcripts of PBMCs from 10 children with allergic asthma. We obtained 558 functional IgG4 sequences, of which 286 were unique. Compared with previously published unique IgE transcripts from the same blood samples, the somatic mutation rate was significantly enhanced in IgG4 transcripts (62 versus 83%; p < 0.001), whereas fewer IgG4 sequences displayed statistical evidence of Ag-driven selection (p < 0.001). On average, the hypervariable CDRH3 region was four nucleotides shorter in IgG4 than in IgE transcripts (p < 0.001). IgG4 transcripts in the circulation of children with allergic asthma reflect some characteristics of classical Ag-driven B2 immune responses but display less indication of Ag selection than do IgE transcripts. Although allergen-specific IgG4 can block IgE-mediated allergen presentation and degranulation of mast cells, key factors that influence the Ag-binding properties of the Ab differ between the overall repertoires of circulating IgG4- and IgE-expressing cells.

show abstract

Immunoglobulin Analysis Tool: A Novel Tool for the Analysis of Human and Mouse Heavy and Light Chain Transcripts

Cited by 67 publications

References 78 publications

Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells

Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding VH81X-expressing B cells

CD4+ T Cells and CD40 Participate in Selection and Homeostasis of Peripheral B Cells

IgG4 and IgE Transcripts in Childhood Allergic Asthma Reflect Divergent Antigen-Driven Selection

Contact Info

Product

Resources

About