NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity.

Moore DJ, Noorchashm H, Lin TH, Greeley SA, Naji A
Diabetes. 2005 54 (7): 2019-25

PMID: 15983202 · DOI:10.2337/diabetes.54.7.2019

Although it is well established that B-cells are required for the development of diabetes in the nonobese diabetic (NOD) mouse, the nature of their role remains unknown. Herein, we investigate the hypothesis that B-cells in this autoimmune background actively disrupt the tolerant state of those T-cells with which they interact. We demonstrate that NOD B-cells express elevated levels of crucial molecules involved in antigen presentation (including CD21/35, major histocompatibility complex class II, and CD40), alterations that invite the possibility of inappropriate T-cell activation. However, when chimeric animals are generated in which all B-cells are NOD-derived, a tolerant state is maintained. These data demonstrate that although B-cells are required for the development of autoimmunity, they are not sufficient to disrupt established tolerance. Moreover, non-B-cell antigen-presenting cells may be the critical actors in the establishment of the tolerant state; this function may be absent in NOD mice as they are characterized by deficient professional antigen-presenting cell function.

MeSH Terms (15)

Animals Antigen-Presenting Cells Antigens, Differentiation Autoimmunity B-Lymphocytes Cell Division Chimera Diabetes Mellitus Histocompatibility Antigens Class II Islets of Langerhans Mice Mice, Inbred C57BL Mice, Inbred NOD Mice, Inbred Strains T-Lymphocytes

Connections (1)

This publication is referenced by other Labnodes entities: