Reduced diabetes in btk-deficient nonobese diabetic mice and restoration of diabetes with provision of an anti-insulin IgH chain transgene

Peggy L. Kendall, Daniel J. Moore, Chrys Hulbert, Kristen L. Hoek, Wasif Khan, James W. Thomas

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Type 1 diabetes results from T cell-mediated destruction of insulin-producing β cells. Although elimination of B lymphocytes has proven successful at preventing disease, modulation of B cell function as a means to prevent type 1 diabetes has not been investigated. The development, fate, and function of B lymphocytes depend upon BCR signaling, which is mediated in part by Bruton's tyrosine kinase (BTK). When introduced into NOD mice, btk deficiency only modestly reduces B cell numbers, but dramatically protects against diabetes. In NOD, btk deficiency mirrors changes in B cell subsets seen in other strains, but also improves B cell-related tolerance, as indicated by failure to generate insulin autoantibodies. Introduction of an antiinsulin BCR H chain transgene restores diabetes in btk-deficient NOD mice, indicating that btk-deficient B cells are functionally capable of promoting autoimmune diabetes if they have a critical autoimmune specificity. This suggests that the disease-protective effect of btk deficiency may reflect a lack of autoreactive specificities in the B cell repertoire. Thus, signaling via BTK can be modulated to improve B cell tolerance, and prevent T cell-mediated autoimmune diabetes.

Original languageEnglish
Pages (from-to)6403-6412
Number of pages10
JournalJournal of Immunology
Volume183
Issue number10
DOIs
StatePublished - Nov 15 2009

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Inbred NOD Mouse
Transgenes
B-Lymphocytes
Insulin
Type 1 Diabetes Mellitus
B-Lymphocyte Subsets
T-Lymphocytes
Autoantibodies
Cell Count

ASJC Scopus subject areas

  • Immunology

Cite this

Reduced diabetes in btk-deficient nonobese diabetic mice and restoration of diabetes with provision of an anti-insulin IgH chain transgene. / Kendall, Peggy L.; Moore, Daniel J.; Hulbert, Chrys; Hoek, Kristen L.; Khan, Wasif; Thomas, James W.

In: Journal of Immunology, Vol. 183, No. 10, 15.11.2009, p. 6403-6412.

Research output: Contribution to journalArticle

Kendall, Peggy L. ; Moore, Daniel J. ; Hulbert, Chrys ; Hoek, Kristen L. ; Khan, Wasif ; Thomas, James W. / Reduced diabetes in btk-deficient nonobese diabetic mice and restoration of diabetes with provision of an anti-insulin IgH chain transgene. In: Journal of Immunology. 2009 ; Vol. 183, No. 10. pp. 6403-6412.
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