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. 2005 Fall;2(3):121-35.
doi: 10.1900/RDS.2005.2.121. Epub 2005 Nov 10.

B cells in autoimmune diabetes

F Susan Wong  1 , Li Wen
Affiliations

B cells in autoimmune diabetes

F Susan Wong et al. Rev Diabet Stud. 2005 Fall.

Abstract

Autoantibodies have been used as good markers for the prediction of future development of type 1 diabetes mellitus (T1DM), but are not thought to be pathogenic in this disease. The role of B cells that produce autoantibodies in the pathogenesis of human T1DM is largely unknown. In the non-obese diabetic (NOD) mouse model of autoimmune diabetes, it has been shown that B cells may contribute multifariously to the pathogenesis of the disease. Some aspects of deficiencies of B cell tolerance may lead to the circulation of autoreactive B cells. In addition, the antigen-presenting function of autoantigen specific B cells is likely to be particularly important, and autoantibodies are also considered to play a critical role. This review discusses the possible aspects of B cells involved in the development of autoimmune diabetes.

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Figures

Figure 1
Figure 1. B cell and CD4 T cell interaction
A. Naïve T cells are generally primed by antigen-presenting cells such as dendritic cells. B. Antigen-specific T cells recognizing antigens presented by B cells stimulate the B cells through CD40 ligand (CD40L) interactions with CD40. C. Activated B cells upregulate costimulatory molecules such as B7.2 and B7.1 which are then able to stimulate T cells. D. T cells activated by specific antigen-recognition together with costimulation produce cytokines. E. T cell-derived cytokines stimulate B cells to switch isotypes and differentiate to produce antibodies.
Figure 2
Figure 2. Generation of NOD mice that have a class II deficiency on the B cells (NOD.BCIID mice)
NOD mice were crossed with I-Ab-/- B6 mice on the H-2b genetic background (KbDb) to generate NOD mice expressing the class II knockout mutation. Since MHC class I is in strong linkage disequilibrium with MHC class II, the introduction of the MHC class II knockout mutation introduces not only I-Ab-/- but also alters the MHC class I molecules of the NOD haplotype (KdDb) to KbDb. NOD female mice then were irradiated and reconstituted with bone marrow from these NOD.I-Ab-/- mice and NOD.µMT-/- mice. This generated mice that had T cells and non-B cell antigen-presenting cells from both NOD I-Ab-/- mice and NOD.µMT-/- mice. Therefore, the resulting mice expressed the NOD I-Ag7 (derived from the NOD.µMT-/- mice) on the non-B cell antigen-presenting cells. However, in the B cell compartment, the mice would only express B cells from the NOD I-Ab-/- mice as NOD.µMT-/- mice do not have mature B cells. Thus the B cells would not express MHC class II and the MHC class I molecules are de-rived from the H-2b haplotype. All the other cells in the NOD BCIID mice express MHC molecules of both H-2g7 (KdDbI-Ag7) and I-Ab-/- (KbDb) haplotypes.
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