Data from The B-cell Receptor Blueprint in Lymphoma: Mechanisms and Therapeutic Opportunities

<div>Abstract<p>The B-cell receptor (BCR) is central to normal and malignant B-cell biology, integrating intrinsic programs with microenvironmental cues to shape cell fate. Across mature B-cell lymphomas, differences in BCR expression, class, and signaling mode define distinct pathogenetic routes and therapeutic vulnerabilities, ranging from BCR-dependent to BCR-silent states. We propose a BCR blueprint that positions these tumors along a continuum of signaling modes and class-imposed functions, emphasizing germinal center–derived lymphomas. This framework links specific BCR states to genetic lesions and microenvironmental niches, underscoring the value of routinely monitoring BCR features to track tumor evolution and inform therapy.</p>Significance:<p>B-cell lymphomas exploit diverse BCR expression levels, classes, and signaling modes that span BCR-addicted to BCR-silent states and shape their genetic programs and therapeutic dependencies. A unified BCR blueprint reframes these diseases along a continuum of BCR signaling and isotype-driven biology, particularly in germinal center–derived entities. Embedding this blueprint into routine clinical testing has the potential to improve prediction of response or resistance to BCR-targeted and other mechanism–based therapies.</p></div>