Scientists at the Baylor College of Medicine and the University of Michigan Medical School reported that a subset of immune B cells, known as CD19+IgM+ B cells, can delay the onset of type 1 diabetes in a mouse model. These findings open an opportunity to develop novel treatments for a subgroup of diabetes mellitus that affects about 420 million people around the world, according to the researchers whose study (“CD19+IgM+ cells demonstrate enhanced therapeutic efficacy in type 1 diabetes mellitus”) appears in JCI Insight.
“We describe a protective effect on autoimmune diabetes and reduced destructive insulitis in NOD.scid recipients following splenocyte injections from diabetic NOD donors and sorted CD19+ cells compared with NOD.scid recipients receiving splenocytes alone. This protective effect was age-specific (only CD19+ cells from young NOD donors exerted this effect; P < 0.001). We found that the CD19+IgM+ cell is the primary subpopulation of B cells that delayed the transfer of diabetes mediated by diabetogenic T cells from NOD mice (P = 0.002). Removal of IgM+ cells from the CD19+ pool did not result in protection. Notably, the protection conferred by CD19+IgM+ co-transfers were not dependent on the presence of Tregs, as their depletion did not affect their ability to delay the onset of diabetes,” reported the investigators.
“Blockade of IL-10 with neutralizing antibodies at the time of CD19+ cell co-transfers also abrogated the therapeutic effect, suggesting that IL-10 secretion was an important component of protection. These results were strengthened by ex vivo incubation of CD19+ cells with IL-5, resulting in enhanced proliferation and IL-10 production and equivalently delayed diabetes progression (P = 0.0005). The potential to expand CD19+IgM+ cells, especially in response to IL-5 stimulation or by pharmacologic agents, may be a new therapeutic option for type 1 diabetes.”
“For many years, one of the research interests of my lab has been to better understand the role the immune system plays in type 1 diabetes,” said corresponding author Massimo Pietropaolo, M.D., professor of medicine-endocrinology and McNair scholar at Baylor College of Medicine.
Increasing experimental evidence supports an important role of B cells in the development of diabetes, both in animal models and in humans. It’s been shown, for example, that subsets of B cells can directly contribute to disease development.
“However, there are also indications that subsets of B cells may be involved in modulating the onset of the condition,” Dr. Pietropaolo explained. “For instance, elimination of a specific subset of B cells carrying the μ-chain marker resulted in impaired diabetes progression in a mouse model.”
In this study, Dr. Pietropaolo and his colleagues studied in more detail a specific subset of B cells, called CD19+ IgM+ B cells and how they affected the onset of diabetes in a mouse model of the condition. The researchers discovered that when they transferred CD19+ IgM+ B cells to the mice, they were able to delay diabetes onset. The protective effect seems to be age specific. CD19+ IgM+ B cells from 6-week-old mice delayed diabetes onset, unlike CD19+ IgM+ B cells from mice older than 15 weeks.
“We are the first to describe that CD19+ IgM+ B cells play a strong regulatory effect that delays diabetes onset in a mouse model,” noted Dr. Pietropaolo. “Taken together, our results open the future possibility of developing new therapies for this disease by expanding this specific B cell subtype pharmacologically and in turn modulating their regulatory actions in ways that would interfere with the onset of type 1 diabetes.”
