Lamin B1 safeguards the B cell genome and shapes lymphoma outcome

作者：Filip Filipsky, Katarina B. Chapman, Johannes Bloehdorn, Oscar Maiques, Abigail Lee, Andrew Clear, Jun Wang, John G. Gribben, Michael Joseph Hausmann, Christoph Cremer, Andrejs Braun, Marta Crespi Sallan, Tetyana Klymenko · 发表于：HemaSphere · 年份：2026 · DOI：10.1002/hem3.70387 · 被引用次数：1 · 研究领域：Nuclear Structure and Function、Cell Adhesion Molecules Research、Skin and Cellular Biology Research

Lamin B1 is a structural component of the nuclear lamina that participates in genome organization and transcriptional control. During adaptive immune responses, B lymphocytes in germinal centers (GCs) undergo clonal expansion and programmed DNA damage at immunoglobulin loci, while simultaneously downregulating Lamin B1. Likewise, Lamin B1 downregulation has been observed in GC-derived lymphomas and myeloid malignancies, yet the functional consequences of Lamin B1 loss during B cell development remain poorly understood. Here, we used in vivo and in vitro B cell models of conditional hypomorphic Lamin B1 expression, which showed elevated DNA damage and disrupted transcriptional profiles. Using sBLISS (in situ labeling and sequencing of double-strand breaks), we identified nonrandom double-strand break hotspots in both mouse and human GC B cells depleted of Lamin B1. These breaks are preferentially located near transcriptional start sites (TSSs) and regulatory elements that control translation and mRNA fate, suggesting Lamin B1 has a role in protecting regulatory genomic regions. Moreover, low LMNB1 expression is associated with poor clinical outcomes in patients with diffuse large B-cell lymphoma (DLBCL). Together, this study reveals a crucial role for Lamin B1 in preserving genomic stability in B cells, underscoring its impact on the pathogenesis of B cell-derived malignancies.