A fraction of chronic lymphocytic leukaemia (CLL) cases carry highly homologous B-cell receptors (BCR), i.e. characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity determining region-3 (HCDR3), often associated with a restricted selection of IGVK/L light chains. Such 'stereotyped' BCR occur more frequently in CLL with unmutated (UM) than mutated (M) IGHV genes. We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time-to-treatment (TTT) and presence of known prognosticators. Sixty-nine clusters (319 IG-rearrangements, 22.4%) with stereotyped BCR were identified. Among 30 confirmed clusters (>or=3 IG-rearrangements/cluster), we found 14 novel clusters, of which 11 had M IG rearrangements (M clusters) and predominantly (8/11) used IGHV3 subgroup genes. Recurrent cluster-biased amino acid changes were found throughout IGHV sequences of these 'M clusters'. Regarding clinical outcome: (i) UM CLL from the IGHV1-2/1-3/1-18/1-46/7-4-1/IGKV1-39 cluster had poorer prognosis than UM/M cases, or UM cases using the same IGHV genes but not in clusters; (ii) M CLL from the IGHV3-21/IGLV3-21 cluster had TTT similar to UM CLL, and shorter than M CLL expressing IGHV3-21 but not in cluster. Altogether, our analysis identified additional molecular and clinical features for CLL expressing stereotyped BCR.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1365-2141.2008.07469.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Atypical memory B cells from natural malaria infection produced broadly neutralizing antibodies against Plasmodium vivax variants.
PLoS Pathog
January 2025
Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Expansion of atypical memory B cells (aMBCs) was demonstrated in malaria-exposed individuals. To date, the generation of P. vivax-specific aMBCs and their function in protective humoral immune responses is unknown.
View Article and Find Full Text PDFAn allelic atlas of immunoglobulin heavy chain variable regions reveals antibody binding epitope preference resilient to SARS-CoV-2 mutation escape.
Front Immunol
January 2025
State Key Laboratory of Respiratory Disease, Guangdong Laboratory of Computational Biomedicine, Center for Cell Lineage Research, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Background: Although immunoglobulin (Ig) alleles play a pivotal role in the antibody response to pathogens, research to understand their role in the humoral immune response is still limited.
Methods: We retrieved the germline sequences for the IGHV from the IMGT database to illustrate the amino acid polymorphism present within germline sequences of IGHV genes. We aassembled the sequences of IgM and IgD repertoire from 130 people to investigate the genetic variations in the population.
Novel rhesus macaque immunoglobulin germline genes identified by three sequencing approaches.
Front Immunol
January 2025
Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, United States.
Introduction: Rhesus macaques have long been a focus of research for understanding immune responses to human pathogens due to their close phylogenetic relationship with humans. As rhesus macaque antibody germlines show high degrees of polymorphism, the spectrum of database-covered genes expressed in individual macaques remains to be determined.
Methods: Here, four rhesus macaques infected with SHIV became a study of interest because they developed broadly neutralizing antibodies against HIV-1.
Insights into genetic aberrations and signalling pathway interactions in chronic lymphocytic leukemia: from pathogenesis to treatment strategies.
Biomark Res
December 2024
L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolf Weigl 12, 53-114, Wroclaw, Poland.
Chronic lymphocytic leukemia (CLL) is prevalent in adults and is characterized by the accumulation of mature B cells in the blood, bone marrow, lymph nodes, and spleens. Recent progress in therapy and the introduction of targeted treatments [inhibitors of Bruton's tyrosine kinase (BTKi) or inhibitor of anti-apoptotic B-cell lymphoma-2 (Bcl-2i) protein (venetoclax)] in place of chemoimmunotherapy have significantly improved the outcomes of patients with CLL. These advancements have shifted the importance of traditional predictive markers, leading to a greater focus on resistance genes and reducing the significance of mutations, such as TP53 and del(17p).
View Article and Find Full Text PDFMutability and hypermutation antagonize immunoglobulin codon optimality.
Mol Cell
January 2025
Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!