Target to B!

B-cells are an essential arm of adaptive immunity-in-balance, as their differentiation in response to foreign antigen generates protective immunological memory and antibodies. When out of balance, aberrant B-cell differentiation and escape from immunological checkpoints governing tolerance and B-cell-selection/activation may lead to pathological, autoreactive, immunological memory and (auto)antibodies. As a result a wide array of immune-mediated diseases (B-IMDs) or malignant transformation of B-cells may follow. Ample evidence indicates successful therapeutic targeting of the B-cell→plasmacell→antibody axis in autoimmune diseases and hematological malignancies. Since almost 10% of the population suffers from either IMDs or lymphoma/leukemia in the Netherlands, there is urgent need for combining B-cell biology expertises across disease fields to optimize therapy efficacy within the fields of B-IMDs and B-cell/plasmacell malignancies. Oncological experience will cross-fertilize and improve IMD treatment approaches possibly leading to cure. IMD-derived B-cell knowledge will fuel development of new treatment strategies in oncology.

Our B-cell consortium represents a national interdisciplinary platform that combines basic and translational B-cell research aiming to understand B-cell derailment and to improve B-cell-targeted therapies in partnership with industry and a patient-advisory-board.

We will cooperatively investigate how normal B cell development gets out-of-balance (by deep-phenotyping, repertoire-analysis, multi-omics, functional studies, data-mining), harmonize ongoing studies in several distinct diseases, develop and apply state-of-the-art immunomonitoring, and combine shared bioinformatics and datamanagement. Our over-arching platform will assess common ánd individual B-cell targets, identify biomarkers predicting therapy-outcomes and allow improved patient stratification for optimized therapies, acting as central hub to disseminate novel B-cell-directed therapies including vaccination strategies, and evaluation thereof.