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http://purl.uniprot.org/citations/31444529http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/31444529http://www.w3.org/2000/01/rdf-schema#comment"

Aims/hypothesis

Autoreactive B cells escape immune tolerance and contribute to the pathogenesis of type 1 diabetes. While global B cell depletion is a successful therapy for autoimmune disease, the fate of autoreactive cells during this treatment in autoimmune diabetes is unknown. We aimed to identify and track anti-insulin B cells in pancreatic islets and understand their repopulation after anti-CD20 treatment.

Methods

We generated a double transgenic system, the VH125.hCD20/NOD mouse. The VH125 transgenic mouse, expressing an increased frequency of anti-insulin B cells, was crossed with a human CD20 (hCD20) transgenic mouse, to facilitate B cell depletion using anti-CD20. B cells were analysed using multiparameter and ImageStream flow cytometry.

Results

We demonstrated that anti-insulin B cells were recruited to the pancreas during disease progression in VH125.hCD20/NOD mice. We identified two distinct populations of anti-insulin B cells in pancreatic islets, based on CD19 expression, with both populations enriched in the CD138int fraction. Anti-insulin B cells were not identified in the plasma-cell CD138hi fraction, which also expressed the transcription factor Blimp-1. After anti-CD20 treatment, anti-insulin B cells repopulated the pancreatic islets earlier than non-specific B cells. Importantly, we observed that a CD138intinsulin+CD19- population was particularly enriched after B cell depletion, possibly contributing to the persistence of disease still observed in some mice after anti-CD20 treatment.

Conclusions/interpretation

Our observations may indicate why the loss of C-peptide is only temporarily delayed following anti-CD20 treatment in human type 1 diabetes."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.org/dc/terms/identifier"doi:10.1007/s00125-019-04974-y"xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/author"Davies J."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/author"Wen L."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/author"Wong F.S."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/author"Buckingham L."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/author"Boldison J."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/author"Da Rosa L.C."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/date"2019"xsd:gYear
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/name"Diabetologia"xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/pages"2052-2065"xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/title"Phenotypically distinct anti-insulin B cells repopulate pancreatic islets after anti-CD20 treatment in NOD mice."xsd:string
http://purl.uniprot.org/citations/31444529http://purl.uniprot.org/core/volume"62"xsd:string
http://purl.uniprot.org/citations/31444529http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/31444529
http://purl.uniprot.org/citations/31444529http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/31444529
http://purl.uniprot.org/uniprot/#_P01849-mappedCitation-31444529http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/31444529
http://purl.uniprot.org/uniprot/P01849http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/31444529