B-1 cells produce insulin and abrogate experimental streptozotocin-induced diabetes

Eur J Immunol. 2015 May;45(5):1452-61. doi: 10.1002/eji.201445409. Epub 2015 Apr 17.

Abstract

The participation of B-1 cells in a murine model of spontaneous diabetes has been recently reported. Here, we describe the role of B-1 cells in streptozotocin (STZ) induced diabetes in mice. We demonstrated that XID (B-1 cell-deficient) mice are more susceptible to STZ treatment than WT mice, as evidenced by their higher blood glucose level in response to STZ. Unexpectedly, the XID mice that were i.p. transferred with purified B-1 cells, either before or after the STZ treatment, did not develop diabetes. These cell transfers provided long-lasting protection for the XID mice against STZ-induced diabetes, suggesting that B-1 cells play an important role in the experimental diabetes pathobiology. We also showed that B-1 cell culture supernatants were able to regulate the blood glucose level of the diabetic XID mice, and we identified insulin-producing cells when B-1 cells were differentiated in B-1 cell-derived phagocyte in vitro. These findings provide a novel role for B-1 cells in metabolic processes, presenting a new mechanism to explain the pathogenesis of diabetes and a possible therapeutical target.

Keywords: B-1 cells; Experimental diabetes; Insulin; Streptozotocin; XID mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Agammaglobulinaemia Tyrosine Kinase
  • Animals
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Experimental / etiology
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / prevention & control*
  • Insulin / biosynthesis*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Pancreas / pathology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology
  • Streptozocin / administration & dosage
  • Streptozocin / toxicity

Substances

  • Blood Glucose
  • Insulin
  • Streptozocin
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • Btk protein, mouse