Clinical Immunology · 2017 · 42 citations · 63 references
Life SciencesCell BiologyImmunologyAutoimmunityClinical ImmunologyDevelopmental ImmunologyB Cell ActivationB Cell BiologyB Cell DevelopmentDiabetes MellitusImmune MaturationLymphocyte DevelopmentB Cell Subset BiologyB Cell Tolerance CheckpointsB-cell DisordersB-cell ImmunophenotypesFas Receptor SignalingIndividualized TherapyMature B Cell DifferentiationTransitional B Cell Maturation
Although autoantibodies have been used for decades as diagnostic and prognostic markers in type 1 diabetes (T1D), further analysis of developmental abnormalities in B cells could reveal tolerance checkpoint defects that could improve individualized therapy. To evaluate B cell developmental progression in T1D, immunophenotyping was used to classify circulating B cells into transitional, mature naïve, mature activated, and resting memory subsets. Then each subset was analyzed for the expression of additional maturation-associated markers. While the frequencies of B cell subsets did not differ significantly between patients and controls, some T1D subjects exhibited reduced proportions of B cells that expressed transmembrane activator and CAML interactor (TACI) and Fas receptor (FasR). Furthermore, some T1D subjects had B cell subsets with lower frequencies of class switching. These results suggest circulating B cells exhibit variable maturation phenotypes in T1D. These phenotypic variations may correlate with differences in B cell selection in individual T1D patients.
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TACI and BCMA are receptors for a TNF homologue implicated in B-cell autoimmune disease
Jane A. Gross, Janet Johnston, Sherri Mudri et al. · Nature · 2000 · 1.2K citations