Biology subjects

Gornitzka, M. B.

Publications and source records attributed to Gornitzka, M. B..

3 recordsLinked to original sources

bioRxiv2026

Putative target antigens of the stereotyped intrathecal B cell response in multiple sclerosis

Intrathecal antibody production is a hallmark of multiple sclerosis (MS), yet the antigenic targets of these antibodies remain elusive. Intrathecal antibody-secreting cells in MS patients characteristically produce IgG1 antibodies carrying the G1m1 allotype and preferentially use IGHV4 heavy-chain genes paired with IGKV1 or IGKV3 light chains. This stereotyped pattern points to a common antigen-driven selection process. To test this hypothesis, we generated monoclonal antibodies from intrathecal B-lineage cells bearing this stereotyped B-cell receptor configuration and screened them against a comprehensive library of human and Epstein-Barr virus proteins. In parallel, we developed and validated an immunoprecipitation-tandem mass-spectrometry (IPMS/MS) workflow for fresh-frozen brain tissue that preserves conformational epitopes. Several proteins, like CLDN11 and PLD1, were enriched by antibodies from multiple patients. Other targets, like MED21 and GIPC2, were unique to individual patients. Our study delivers a scalable pipeline for antigen discovery in MS and nominates candidate antigens for future validation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=167 SRC="FIGDIR/small/697481v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@b522eaorg.highwire.dtl.DTLVardef@76240org.highwire.dtl.DTLVardef@c36205org.highwire.dtl.DTLVardef@1587019_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

GATHeR: Graph-based Accurate Tool for Immunoglobulin HEavy- and Light-chain Reconstruction

Recovering full-length, paired B-cell receptor (BCR) sequences from scRNA-seq reads remains difficult, especially in naive and memory B cells where immunoglobulin transcripts are sparse. Current methods provide incomplete constant-region coverage, limiting isoform, subclass, and allele resolution. We present GATHeR, an open-source tool that assembles and annotates paired heavy- and light-chain BCR sequences and extends assembled sequences into constant regions. This enables confident subclass and allele assignment and recovery of the membrane-bound isoform, including the transmembrane segment and cytoplasmic tail, thereby distinguishing surface BCRs from secreted antibodies. GATHeR supports Smart-seq2/3 and 10x Genomics libraries and outperforms existing methods across benchmarks, with the largest gains in naive and memory B cells. Notably, in these populations the constant-region extension also revealed splice variation, including heavy-chain intron retention. By delivering high-fidelity receptor, isoform, and clonal lineage information, GATHeR broadens the analytical reach of scRNA-seq for B-cell immunology.

immunology↗

bioRxiv2024

Ultra-long sequencing for contiguous haplotype resolution of the human immunoglobulin heavy chain locus

Genetic diversity within the human immunoglobulin heavy chain (IGH) locus influences the expressed antibody repertoire and susceptibility to infectious and autoimmune diseases. However, repetitive sequences and complex structural variation pose significant challenges for large-scale characterization. Here, we introduce a method using Oxford Nanopore ultra-long sequencing and adaptive sampling, coupled with a bioinformatic pipeline, to generate haplotype-resolved single-contig IGH assemblies. We compared our method to a well-established IGH characterization framework using Pacific Biosciences HiFi sequencing in four donors and observed almost complete sequence congruence between our haplotype-resolved assemblies and the HiFi reads. Applying our approach to the HG002 reference material revealed no base differences to the Telomere-to-Telomere genome benchmark over the IGH locus. Importantly, among the four donors, our approach uncovered 30 novel alleles and previously uncharacterized large structural variants, including a 120 kb segmental duplication spanning IGHE to IGHA1 and an expanded seven-copy IGHV3-23 gene haplotype.

immunology↗