Marvyn Koning

Marvyn Koning
Leiden University Medical Center · Department of Hematology

M.D.

About

30
Publications
2,800
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251
Citations
Additional affiliations
September 2013 - March 2017
Leiden University Medical Center
Position
  • PhD Student

Publications

Publications (30)
Article
Full-text available
Upon antigen recognition, activation-induced cytosine deaminase initiates affinity maturation of the B-cell receptor by somatic hypermutation (SHM) through error-prone DNA repair pathways. SHM typically creates single nucleotide substitutions, but tandem substitutions may also occur. We investigated incidence and sequence context of tandem substitu...
Article
Upon antigen recognition, activation-induced cytosine deaminase initiates affinity maturation of the B-cell receptor by somatic hypermutation (SHM) through error-prone DNA repair pathways. SHM typically creates single nucleotide substitutions, but tandem substitutions may also occur. While tandem substitutions have been described in mice and other...
Article
Full-text available
The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In a...
Article
Full-text available
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 domai...
Article
Objectives: Follicular lymphoma (FL) typically originates from premalignant mature B cells that carry the founder t(14;18) BCL2 translocation. Mutations in epigenetic modifiers and acquisition of N-glycosylation sites in CDR regions of the B-cell receptor (BCR) are recurrent secondary events in FL pathogenesis. Despite these oncogenic drivers, FL c...
Article
Full-text available
Many autoimmune diseases are hallmarked by autoreactive B and plasma cell responses that are directly or indirectly involved in disease pathogenesis. These B-cell responses show large variability between diseases, both in terms of the secreted autoantibody repertoire and the dynamics and characteristics of the underlying B-cell responses. Hence, di...
Article
Full-text available
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, tem...
Article
Full-text available
Objective To isolate and characterize muscle-specific kinase (MuSK) monoclonal antibodies from patients with MuSK myasthenia gravis (MG) on a genetic and functional level. Methods We generated recombinant MuSK antibodies from patient-derived clonal MuSK-specific B cells and produced monovalent Fab fragments from them. Both the antibodies and Fab f...
Article
Full-text available
Primary cutaneous follicle center lymphoma (PCFCL) is a rare mature B-cell lymphoma with an unknown etiology. PCFCL resembles follicular lymphoma (FL) by cytomorphologic and microarchitectural criteria. FL B cells are selected for N-linked glycosylation motifs in their B-cell receptors (BCRs) that are acquired during continuous somatic hypermutatio...
Article
Full-text available
Purpose Anterior cervical discectomy and fusion (ACDF) has proven effective in treating radicular arm pain. Post-operatively, cervical spine stability is temporarily challenged, but data on bony fusion and speed of fusion are ambiguous; optimum evaluation method and criteria are debated. Aim To study bony fusion accomplishment and to obtain an ove...
Article
Full-text available
A 21-year-old female presented with headache, nausea and vomiting, dysarthria, difficulty finding words, vertigo, episodical diplopia and an abnormal gait since 2 days. Additionally, we found marked ataxia and disturbed liver chemistry whilst her infection parameters were low. Her head CT scan was unremarkable, but her MRI scan showed leptomeningea...
Article
Introduction & Objectives: Primary Cutaneous Follicle Center Lymphoma (PCFCL) is a very indolent mature B-cell lymphoma that shares germinal center morphology with follicular lymphoma (FL) but lacks the characteristic t(14;18). Unlike FL, immunohistochemistry fails to detect expression of BCL2, CD10, and immunoglobulin in PCFCL. Therefore, we inves...
Conference Paper
Full-text available
Background Anti-citrullinated protein antibodies (ACPA) represent the most specific biomarker in Rheumatoid Arthritis (RA) and have been associated with RA pathogenesis. ACPA-IgG are heavily N-glycosylated in the variable domain. Recently, we showed that>80% of ACPA-IgG clones harbour N-glycosylation sites in their variable regions that result from...
Article
Full-text available
Background: The placement of intervertebral cages in anterior cervical discectomy (ACDF) supposedly maintains foraminal height. The most commonly reported cage-related complication is subsidence, although it is unknown whether a correlation between subsidence and clinical outcome exists. Aim: To assess the incidence and relevance of subsidence....
Conference Paper
Background Recent structural analysis of anti citrullinated protein antibodies (ACPA) in serum and synovial fluid of patients with rheumatoid arthritis (RA) revealed that the vast majority (>90%) of secreted ACPA IgG molecules carry N-glycans in the variable (Fab) domain. This remarkable degree of Fab-glycosylation is absent from ACPA-depleted cont...
Conference Paper
Full-text available
Background Primary mediastinal large B-cell lymphoma (PM LBCL) is putatively derived from thymic B cells. PM LBCL is clinically and morphologically distinct from diffuse large B-cell lymphoma (DLBCL), but shares certain phenotypic characteristics with nodular sclerosing classical Hodgkin's lymphoma. The expression and function of an intact B-cell...
Article
Full-text available
Background The activated B-cell (ABC) type of diffuse large B-cell lymphoma (DLBCL) is clinically more aggressive than the germinal center (GCB) type. The gene expression profile of ABC DLBCL resembles that of mature B cells upon stimulation via their B-cell receptor (BCR). In app. 10% of ABC DLBCL cases, this signature can be explained by gain-of-...
Article
Full-text available
Background Primary mediastinal large B-cell lymphoma (PM LBCL) is putatively derived from thymic B cells. PM LBCL is clinically and morphologically distinct from diffuse large B-cell lymphoma (DLBCL), but shares certain phenotypic characteristics with nodular sclerosing classical Hodgkin's lymphoma. The expression and function of an intact B-cell r...
Conference Paper
T cells recognizing solid tumors and Hodgkin's lymphoma can be released from anergy by immune checkpoint inhibitors. Its therapeutic success seems to be associated with the abundance of neoepitopes within the tumor mutanome. In neoplastic B cells, VDJ recombination and somatic hypermutation (SHM) generate unique immunoglobulin (Ig) peptide sequence...
Article
Introduction & Objectives: Primary Cutaneous Follicle Center Lymphoma (PCFCL) is a very indolent mature B-cell lymphoma that shares germinal center (GC) morphology with follicular lymphoma (FL) but lacks the characteristic t(14;18). Unlike FL, immunohistochemistry fails to detect expression of BCL2, CD10, and immunoglobulin in PCFCL. We investigate...
Conference Paper
Full-text available
The activated B-cell (ABC) type of diffuse large B-cell lymphoma (DLBCL) is clinically more aggressive than the germinal center (GCB) type. The gene expression profile of ABC DLBCL resembles that of mature B cells upon stimulation via their B-cell receptor (BCR). In up to 30% of ABC DLBCL cases, this signature can be explained by gain-of-function m...
Article
Peptides of the B-cell receptor (BCR) may be presented in HLA molecules and therefore be recognized as epitopes by T cells. Bioinformatic evidence indicates that follicular lymphoma cells are selected against expression of a clonal BCR with a high cumulative predicted binding of BCR-derived peptides to the respective patient's HLA complex (Strothme...
Article
Full-text available
We describe an alternative strategy to multiplex PCR for sequencing and cloning of lymphoma-derived immunoglobulin receptors and potentially for unbiased full B-cell repertoire sequencing.

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Projects (3)
Project
Follicular lymphoma is an indolent malignancy of mature B cells that are subject to ongoing somatic hypermutation. In this project we investigate the role genome wide mutations in the progression of the disease.