Abstract

Objective: To determine the role of B cells in promoting CD8⁺ T cell-mediated β cell destruction in chronically inflamed islets.

Research Design and Methods: RIP-TNFα-NOD mice were crossed to B cell deficient NOD mice and diabetes development monitored. In vitro antigen presentation assays, in vivo administration of the bromodeoxyuridine coupled to flow cytometry assays assessed intra-islet T cell activation in the absence or presence of B cells. CD4⁺Foxp3⁺ activity in the absence or presence of B cells was tested using in vivo depletion techniques. Cytokine production and apoptosis assays determined the capacity of CD8⁺ T cells transform to CTL and survive within inflamed islets in the absence or presence of B cells.

Results: B cell deficiency significantly delayed diabetes development in chronically inflamed islets. Re-introduction of B cells incapable of secreting Ig restored diabetes development. Both CD4⁺ and CD8⁺ T cell activation was unimpaired by B cell deficiency and delayed disease was not due to CD4⁺Foxp3⁺ T cell suppression of T cell responses. Instead at the CTL transition stage, B cell deficiency resulted in apoptosis of intra-islet CTL.

Conclusion: In inflamed islets, B cells are central for the efficient intra-islet survival of CTL thereby promoting type 1 diabetes development.