Template-switching anchored polymerase chain reaction reliably amplifies functional lambda light chain transcripts of malignant lymphoma

Koning, Marvyn T.; Nteleah, Valeri; Veelken, Hendrik; Navarrete, Marcelo A.

doi:10.3109/10428194.2013.828353

Cited by 12 publications

(11 citation statements)

References 11 publications

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“…TCR-β transcripts were identified using ARTI-SAN PCR adapted for TCR (40,41). Briefly, mRNA was isolated from T cell clones or purified CD8 T cells from PBMCs using magnetic beads (Dynabead mRNA DIRECT Kit; Invitrogen, Thermo Fisher Scientific).…”

Section: Methodsmentioning

confidence: 99%

Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

Bergen¹,

Luxemburg-Heijs²,

Wreede³

et al. 2017

Journal of Clinical Investigation

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Section: Methodsmentioning

confidence: 99%

Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

Bergen¹,

Luxemburg-Heijs²,

Wreede³

et al. 2017

Journal of Clinical Investigation

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“…The novel hypothesis of a specific role of N-glycosylation in expansion and maintenance of IgE-expressing B cells in non-allergic individuals warrants further studies. Ubiquitous NLGM acquisition could have a disease-specific role in selection of IgE-expressing B-cells in similarity to follicular lymphoma (30), primary cutaneous follicle center lymphoma (31) and rheumatoid arthritis (32). On the other hand, glycosylation at NLGM positions could non-specifically obstruct antigen recognition and effectively inhibit BCR affinity maturation (33).…”

Section: Discussionmentioning

confidence: 99%

Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes

et al. 2019

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IgE-mediated allergic disease represents an increasing health problem. Although numerous studies have investigated IgE sequences in allergic patients, little information is available on the healthy IgE repertoire. IgM, IgG, IgA, and IgE transcripts from peripheral blood B cells of five healthy, non-atopic individuals were amplified by unbiased, template-switching, isotype-specific PCR. Complete VDJ regions were sequenced to near-exhaustion on the PacBio platform. Sequences were analyzed for clonal relationships, degree of somatic hypermutation, IGHV gene usage, evidence of antigenic selection, and N-linked glycosylation motifs. IgE repertoires appeared to be highly oligoclonal with preferential usage of certain IGHV genes compared to the other isotypes. IgE sequences carried more somatic mutations than IgM, yet fewer than IgG and IgA. Many IgE sequences contained N-linked glycosylation motifs. IgE sequences had no clonal relationship with the other isotypes. The IgE repertoire in healthy individuals is derived from relatively few clonal expansions without apparent relations to immune reactions that give rise to IgG or IgA. The mutational burden of normal IgE suggests an origin through direct class-switching from the IgM repertoire with little evidence of antigenic drive, and hence presumably low affinity for specific antigens. These findings are compatible with a primary function of the healthy IgE repertoire to occupy Fcε receptors for competitive protection against mast cell degranulation induced by allergen-specific, high-affinity IgE. This background knowledge may help to elucidate pathogenic mechanisms in allergic disease and to design improved desensitization strategies.

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“…When SHM affect off-target genes, it is referred to as aberrant SHM. Aberrant SHM can be mainly detected in FL, BL, DLBCL, and CLL [33][34][35]. This topic has been extensively reviewed elsewhere [36][37][38][39].…”

Section: Somatic Hypermutation (Shm)mentioning

confidence: 99%

The Antigen Receptor as a Driver of B-Cell Lymphoma Development and Evolution

Sepulveda¹,

Seija²,

Oppezzo³

et al. 2018

Hematology - Latest Research and Clinical Advances

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The expression of a functional antigen receptor is necessary for cell survival of normal B lymphocytes and most B-cell neoplasms alike. When the genetic modifications of the B-cell receptor locus fail to produce a functional antigen receptor or result in deleterious mutations of a previously expressed receptor, the affected B cell will undergo apoptosis. The three physiological mechanisms that generate the B-cell receptor, VDJ recombination, somatic hypermutation, and class switch recombination, can induce double-strand DNA breaks and can specifically contribute to lymphomagenesis. On the other hand, the B-cell receptor activation and signaling pathways, which provide strong survival and proliferation signals to normal B cells, can support the growth and evolution of malignant lymphocytes. As a result, an otherwise structurally normal B-cell receptor can behave, from the functional perspective, as a true oncogene. In this chapter, we provide an in-depth discussion of the most recently discovered recurrent mechanisms involving the B-cell receptor in lymphoma pathogenesis. The discussion is structured around two major topics: (1) the genetic mechanisms that create a functional antigen receptor and their errors leading to oncogenic events, and (2) the pathogenic activation of the B-cell receptor signaling cascade. Finally, we will briefly comment on novel emerging therapies targeting the B-cell receptor at different levels.

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Template-switching anchored polymerase chain reaction reliably amplifies functional lambda light chain transcripts of malignant lymphoma

Cited by 12 publications

References 11 publications

Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

Selective graft-versus-leukemia depends on magnitude and diversity of the alloreactive T cell response

Peripheral IgE Repertoires of Healthy Donors Carry Moderate Mutation Loads and Do Not Overlap With Other Isotypes

The Antigen Receptor as a Driver of B-Cell Lymphoma Development and Evolution

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