AIRR-C Seminar Series, March 28th, 2024 - Oscar Rodriguez, University of Louisville, US
4.3 هزار بار بازدید -
3 ماه پیش
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Genome poises antibody repertoire from
Genome poises antibody repertoire from early B cell development
Early Career Speaker: Oscar Rodriguez, University of Louisville
Talk abstract
Unraveling factors that shape the antibody (Ab) repertoire is crucial for understanding adaptive immunity and disease risk. Our study, utilizing long-read genomic and adaptive immune receptor repertoire (AIRR) sequencing, highlighted the significant influence of genetic variation within the immunoglobulin heavy chain locus (IGH) on IgM and IgG Ab repertoires in human peripheral blood mononuclear cells (PBMCs). Extending these findings, we conducted deep AIRR sequencing in six individuals to explore the Ab repertoire across B cell development stages—pro-B, pre-B, immature, and naive. We also sequenced the IGH, IG kappa, and IG lambda loci to create personalized germline allele databases and identify SNPs, indels, and structural variants affecting the Ab repertoire. We found high gene usage correlations across B cell stages and replicated genetic variants in pro-B cells linked to inter-individual variation in the peripheral Ab repertoire, highlighting strong genetic effects on V(D)J recombination. Our analysis revealed associations between IGH variants and specific heavy and light chain gene usage profiles, suggesting trans-effects of IGH locus polymorphisms on light chain repertoire likely due to constraints on chain pairing. Variants correlated with both heavy and light chain usage also significantly influence the CDR3 region variation, including rs74091765, which affects gene usage for IGHV3-64, 13 IGL, and 6 IGK genes, as well as the CDR3 amino acid composition across IGH, IGK, and IGL. Our study demonstrates that genetic variation in the IG loci significantly contributes to Ab repertoire diversity, emphasizing the relevance of IG loci genomics in understanding Ab responses and human disease.
Speaker bio
Oscar Rodriguez is a postdoctoral fellow in the lab of Corey Watson at the University of Louisville School of Medicine. His research focuses on population-level germline immunoglobulin genetic variation and its impact on inter-individual antibody repertoire differences. Recently, he has demonstrated for the first time the significant effect of extensive immunoglobulin germline variation on the antibody repertoire. As a Ph.D. student at the Icahn School of Medicine at Mount Sinai, he developed the first comprehensive tool suite for long-read-based assembly and curation of genetic variation in the immunoglobulin (IG) and T-cell receptor (TCR) loci.
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
Early Career Speaker: Oscar Rodriguez, University of Louisville
Talk abstract
Unraveling factors that shape the antibody (Ab) repertoire is crucial for understanding adaptive immunity and disease risk. Our study, utilizing long-read genomic and adaptive immune receptor repertoire (AIRR) sequencing, highlighted the significant influence of genetic variation within the immunoglobulin heavy chain locus (IGH) on IgM and IgG Ab repertoires in human peripheral blood mononuclear cells (PBMCs). Extending these findings, we conducted deep AIRR sequencing in six individuals to explore the Ab repertoire across B cell development stages—pro-B, pre-B, immature, and naive. We also sequenced the IGH, IG kappa, and IG lambda loci to create personalized germline allele databases and identify SNPs, indels, and structural variants affecting the Ab repertoire. We found high gene usage correlations across B cell stages and replicated genetic variants in pro-B cells linked to inter-individual variation in the peripheral Ab repertoire, highlighting strong genetic effects on V(D)J recombination. Our analysis revealed associations between IGH variants and specific heavy and light chain gene usage profiles, suggesting trans-effects of IGH locus polymorphisms on light chain repertoire likely due to constraints on chain pairing. Variants correlated with both heavy and light chain usage also significantly influence the CDR3 region variation, including rs74091765, which affects gene usage for IGHV3-64, 13 IGL, and 6 IGK genes, as well as the CDR3 amino acid composition across IGH, IGK, and IGL. Our study demonstrates that genetic variation in the IG loci significantly contributes to Ab repertoire diversity, emphasizing the relevance of IG loci genomics in understanding Ab responses and human disease.
Speaker bio
Oscar Rodriguez is a postdoctoral fellow in the lab of Corey Watson at the University of Louisville School of Medicine. His research focuses on population-level germline immunoglobulin genetic variation and its impact on inter-individual antibody repertoire differences. Recently, he has demonstrated for the first time the significant effect of extensive immunoglobulin germline variation on the antibody repertoire. As a Ph.D. student at the Icahn School of Medicine at Mount Sinai, he developed the first comprehensive tool suite for long-read-based assembly and curation of genetic variation in the immunoglobulin (IG) and T-cell receptor (TCR) loci.
AIRR-C Seminar Series website: https://www.antibodysociety.org/the-a...
3 ماه پیش
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