Year: 2026
Type: editorial
Abstract: B cell: faithful models need several cooperating lesions, which is why the field increasingly combines germline alleles with CRISPR-Cas9 editing or retroviral oncogene delivery in bone-marrow chimeras. They argue, equally, that such models must be immunocompetent, because central features of lymphoma biology are invisible in immunodeficient xenograft hosts.Two contributions in this Topic examine settings in which B-cell biology, left unchecked, becomes a driver of non-malignant disease rather than a tool against it. Shimojima et al. 7 review the role of BAFF and APRIL signaling in ANCA-associated vasculitis, showing that persistently elevated BAFF/APRIL levels -and altered expression of their receptors across B-cell subsets -help explain why autoreactive B cells and ANCA production so often re-emerge after rituximab-induced remission, and why combination strategies targeting BAFF/APRIL alongside B-cell depletion are now under active clinical investigation. Nair et al. 8 take a parallel, integrative approach to pre-eclampsia, proposing that toll-like receptor activation, pathogenic B1a cells producing agonistic autoantibodies against the angiotensin II type 1 receptor, and feto-maternal microchimerism do not act independently but form a self-reinforcing immunological circuit that sustains inflammation and impairs placental angiogenesis. Together, these two reviews illustrate a shared lesson: in non-malignant disease, pathology often arises from B-cell abnormal persistence, phenotypic switching, or misdirected specificity -the same molecular handles that engineered B-cell therapies elsewhere in this Topic aim to control deliberately.What unites these five contributions is the B-cell receptor and the antibody it encodes. In the two oncology studies, it is rewritten deliberately to give a B cell a new target. In the lymphoma models, it is a dependency the tumor cannot survive without. In vasculitis and pre-eclampsia, it goes wrong on its own, generating antibodies directed at self. The therapeutic question is therefore the same: which antibody specificities persist, how strongly they signal, and what the cell does in response. This is where the two fields could borrow from each other. The methods used to install a chosen specificity at the IgH locus might equally be used to replace an autoreactive one, rather than deleting the cell that carries it; conversely, what autoimmunity has learned about BAFF and APRIL bears on whether engineered B cells will persist after transfer. The problem is a single one approached from opposite ends: how to control which antibody specificities a B cell carries, and how long they last. Progress will come faster if the fields that engineer B cells and those that study their dysregulation read each other more closely.
Source: Frontiers in Immunology
Authors: Lucia Sereni, Valentina Capo, Francesca Pala
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7221123026