NOD B-cells are insufficient to incite T-cell-mediated anti-islet autoimmunity.
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.
Department of Pediatrics, Vanderbilt Children's Hospital, Vanderbilt University, Nashville, Tennessee, USA.
Daniel J
DJ
Moore
Hooman
H
Noorchashm
Tina H
TH
Lin
Siri A
SA
Greeley
Ali
A
Naji
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002678:Chimera; D003920:Diabetes Mellitus / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology*
D000943:Antigens, Differentiation; D000949:Histocompatibility Antigens Class II