Identification of Immunoglobulin Gene Usage in Immune Repertoires Sequenced by Nanopore Technology

Key Points Mass spectrometry is a high-throughput, low-resource technique that can identify immunoglobulin variable region gene from tissue specimens. IGVL gene usage is restricted and different between systemic and localized AL and only partially explains organ tropism in this disease.

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Common Patterns of B Cell Perturbation and Expanded V4-34 Immunoglobulin Gene Usage in Autoimmunity and Infection

Autoimmunity ◽

10.1080/08916930310001624656 ◽

2004 ◽

Vol 37 (1) ◽

pp. 9-15 ◽

Cited By ~ 28

Author(s):

C. Ian Mockridge ◽

Anisur Rahman ◽

Sarah Buchan ◽

Terry Hamblin ◽

David A. Isenberg ◽

...

Keyword(s):

B Cell ◽

Immunoglobulin Gene ◽

Gene Usage

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Somatic Hypermutation and Diverse Immunoglobulin Gene Usage in the Human Antibody Response to the Capsular Polysaccharide of Streptococcus pneumoniae Type 6B

Infection and Immunity ◽

10.1128/iai.72.6.3505-3514.2004 ◽

2004 ◽

Vol 72 (6) ◽

pp. 3505-3514 ◽

Cited By ~ 39

Author(s):

Jianhui Zhou ◽

Kathleen R. Lottenbach ◽

Stephen J. Barenkamp ◽

Donald C. Reason

Keyword(s):

Streptococcus Pneumoniae ◽

Light Chain ◽

Capsular Polysaccharide ◽

Germ Line ◽

Somatic Hypermutation ◽

Cloning And Expression ◽

Human Antibody ◽

Immunoglobulin Gene ◽

Gene Usage ◽

V Region

ABSTRACT Combinatorial cloning and expression library analysis were used to determine the expressed human antibody repertoire specific for the capsular polysaccharide (PS) of Streptococcus pneumoniae serotype 6B. Sequence analysis of 55 6B-specific antibody Fab fragments isolated from six vaccinated donors reveal that different individuals used a variety of heavy and light chain germ line variable (V) region genes to form pneumococcal capsular PS (PPS) 6B-specific paratopes. Within each donor, however, the response was more restricted, with five of the six donors using at most one or two gene pairs to form combining sites. Analysis also indicated that although the response in each donor was oligoclonal in terms of variable gene usage, the combination of extensive somatic hypermutation, deletion of germ line-encoded residues, insertion of non-germ line-encoded residues, and intraclonal isotype switching generated a surprising degree of paratope diversity within the individuals analyzed. In contrast to previously studied PS-specific responses, we find that the PPS 6B repertoire makes use of a diverse collection of heavy-chain and light-chain V region gene products to form specific paratopes, with no apparent tendency for conservation of immunoglobulin gene usage between individuals.

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Recent Advances in the Genetic of MALT Lymphomas

Cancers ◽

10.3390/cancers14010176 ◽

2021 ◽

Vol 14 (1) ◽

pp. 176

Author(s):

Juan José Rodríguez-Sevilla ◽

Antonio Salar

Keyword(s):

Malt Lymphoma ◽

Genetic Alterations ◽

Clinicopathological Characteristics ◽

Chromosomal Translocations ◽

Immunoglobulin Gene ◽

Gene Usage ◽

Frequent Mutations ◽

Push Forward ◽

Anatomic Locations

Mucosa-associated lymphoid tissue (MALT) lymphomas are a diverse group of lymphoid neoplasms with B-cell origin, occurring in adult patients and usually having an indolent clinical behavior. These lymphomas may arise in different anatomic locations, sharing many clinicopathological characteristics, but also having substantial variances in the aetiology and genetic alterations. Chromosomal translocations are recurrent in MALT lymphomas with different prevalence among different sites, being the 4 most common: t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32). Several chromosomal numerical abnormalities have also been described, but probably represent secondary genetic events. The mutational landscape of MALT lymphomas is wide, and the most frequent mutations are: TNFAIP3, CREBBP, KMT2C, TET2, SPEN, KMT2D, LRP1B, PRDM1, EP300, TNFRSF14, NOTCH1/NOTCH2, and B2M, but many other genes may be involved. Similar to chromosomal translocations, certain mutations are enriched in specific lymphoma types. In the same line, variation in immunoglobulin gene usage is recognized among MALT lymphoma of different anatomic locations. In the last decade, several studies have analyzed the role of microRNA, transcriptomics and epigenetic alterations, further improving our knowledge about the pathogenic mechanisms in MALT lymphoma development. All these advances open the possibility of targeted directed treatment and push forward the concept of precision medicine in MALT lymphomas.

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CHARACTERISTICS OF IMMUNOGLOBULIN GENE USAGE OF THE XENOANTIBODY BINDING TO GAL-??(1,3)GAL TARGET ANTIGENS IN THE GAL KNOCKOUT MOUSE1

Transplantation Journal ◽

10.1097/00007890-200107150-00028 ◽

2001 ◽

Vol 72 (1) ◽

pp. 147-155 ◽

Cited By ~ 23

Author(s):

Satoshi Nozawa ◽

Pei-Xiang Xing ◽

Gordon D. Wu ◽

Eiji Gochi ◽

Mary Kearns-Jonker ◽

...

Keyword(s):

Immunoglobulin Gene ◽

Gene Usage

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Clarifying immunoglobulin gene usage in immunoglobulin light chain amyloidosis by mass spectrometry of amyloid in clinical tissue specimens.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.8605 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 8605-8605 ◽

Cited By ~ 1

Author(s):

Taxiarchis Kourelis ◽

Surendra Dasari ◽

Jason D Theis ◽

Marina Ramirez-Alvarado ◽

Paul J Kurtin ◽

...

Keyword(s):

Mass Spectrometry ◽

Light Chain ◽

Immunoglobulin Gene ◽

Immunoglobulin Light Chain ◽

Light Chain Amyloidosis ◽

Gene Usage ◽

Immunoglobulin Light Chain Amyloidosis ◽

Tissue Specimens

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MLL-AF4 Positive Adult ALL Patients: VH6 Immunoglobulin Gene Rearrangements Predominate While FLT3 Mutations Are Rare.

Blood ◽

10.1182/blood.v104.11.1089.1089 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1089-1089

Author(s):

Veronique M. Duke ◽

Lena Rai ◽

Jeasmin Mortuza ◽

Giuseppe Saglio ◽

Robert Foa ◽

...

Keyword(s):

B Cell ◽

Gene Rearrangement ◽

Tandem Duplication ◽

Fusion Gene ◽

Gene Rearrangements ◽

Immunoglobulin Gene ◽

Internal Tandem Duplication ◽

Poor Outcome ◽

Flt3 Mutations ◽

Gene Usage

Abstract Among patients with adult acute lymphoblastic leukemia (ALL) the t(4;11) translocation (resulting in the MLL-AF4 fusion gene) is a recurrent chromosomal abnormality occurring in approximately 10–15% of cases. It is associated with poor outcome and in the majority of cases stem cell transplantation is the only possible cure. The MLL-AF4 cases show a more immature phenotype than other subtypes frequently lacking Ig light chain and/or TCR gene rearrangements (Brumpt et al; Blood, 2000; 96:2254). We have previously observed that in adult ALL there is a bias towards the use of JH-proximal VH genes and in particular an over-usage of the VH6 gene segment, the most JH-proximal VH element. This is also common in MLL-AF4 patients while rarer in ALL carrying other chromosomal abnormalities (Mortuza et al, 2001; Blood, 97: 2716). VH6 gene usage is also predominant (8–12%) in adult ALL when compared to the mathematical expected VH6 gene usage (0.8%) or the usage observed in normal PB or in other B-cell malignancies, such as CLL (3.6%) and B cell lymphomas (0%). Finally, mutations of FLT3 are detected in a large proportion of acute myeloid leukemias and in a small proportion of childhood ALL carrying the MLL-AF4 fusion gene while it has seldom been observed in adult ALL with t(4;11). The aims of our study were twofold: 1) to expand on the initial observation that the VH6 gene rearrangement may be more frequent in adult patients carrying the t(4;11) translocation; 2). To assess the incidence of FLT3 mutations in an homogenous cohort of adult ALL patients carrying t(4;11) abnormality. Thirty-two cases of MLL-AF4 fusion positive adult ALL patients (17M/15F) were analysed in addition to the RS4;11 cell line. Pro-B phenotype (n=11)predominated. Age ranged between 22–55 yrs(median: 32 yrs). Patients had cytogenetic or molecular evidence of t(4;11). The WBC count at presentation was high (60–550x109/l; median: 220). Patients were tested for VH gene rearrangement using FRI and consensus-JH primers. Internal tandem duplication and codon 835–836 kinase mutations of the FLT3 were screened by DNA PCR analysis. Twenty-seven patients (84%) of the 32 tested carried a VH6 gene rearrangement. Of 36 IgH alleles, 27 (75%) were VH6 rearrangements. VH1 in 4 (11%) rearrangements was the second most common rearrangement while 3 were VH3 (8%) and 2 (5.5%) were VH4. Compared to our previous study (Mortuza et al, 2001; Blood,97:2716) the incidence of VH6 IGH rearrangements in MLL positive cases represents a nine-fold increase (75% vs 9.4%) compared to non-MLL + cases. No Internal Tandem Duplication of the FLT3 gene was detected in the 31 cases tested, while one (3.6%) of the 28 cases analysed showed the recurrent mutation of the Asp835Tyr of the FLT3 gene. In conclusion, patients carrying the t(4;11) translocation show a very skewed pattern of IgH gene rearrangement restricted almost exclusively to the VH6 usage, in agreement with both the more immature B cell phenotype and observation in the mouse immune system. However, in t(4;11) adult ALL FLT3 is rarely found mutated and may therefore play a minor role in the poor outcome of this ALL subgroup.

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