What are B cells?
B cells are a type of immune cell that is present in your blood and circulates throughout your body. Their main role is to help target foreign invaders – viruses, bacteria and other foreign cells – in the body to destroy them in order to prevent disease.
Besides that, B cells have a few different functions. One makes antibodies; another activates other immune cells in the body, such as T cells.
Why do immune cells target pancreatic insulin-producing cells in type 1 diabetes? Can you talk about B cell activation and “anergy”?
Typically, what should happen with the body’s immune cells, such as B cells or T cells, is that they should only recognize foreign invaders as bad and target them for elimination. However, in the case of autoimmunity, immune cells mistakenly think that cells in the body, such as insulin-producing beta cells in the pancreas, are foreign and start attacking them instead. In type 1 diabetes, we believe that B cells inappropriately recognize pancreatic cells as foreign, allowing them to activate. B cells can pick up small pieces of pancreas and show them to T cells in the body. This activates T cells, which then destroy the insulin-producing cells of the pancreas. These attacks on insulin-producing cells lead to type 1 diabetes.
We believe that one of the reasons why type 1 diabetes B cells recognize pancreatic cells as foreign and activate is an impaired anergy.
Anergy is a term we use to describe a self-reactive or self-reactive B cell that is not activated and does not respond to stimulation. That’s a good thing – we don’t want your self-reactive B cells responding. Normally what happens is when a B cell and the body recognize each other – the pancreas, the thyroid gland, etc. – it must be removed or suppressed so that it does not enter the peripheral blood (the blood circulating in the body).
Sometimes this process is not perfect. And even in healthy people, there is sometimes a leak of these self-reactive B cells into the peripheral blood. The way the body controls these cells is through anergy, which is a negative feedback loop telling any self-reactive B cells that have escaped into the peripheral blood to not respond to anything.
How long does it take for the body to go from a failed activated B cell to showing symptoms of type 1 diabetes?
We know that B cells can make antibodies targeting the pancreas years before someone is even diagnosed.
We don’t believe the antibodies themselves are pathogenic, but they are good indicators that the autoimmune process has begun. Even with these indicators, it can take up to years for the insulin-producing cells to be destroyed enough to require exogenous injection (outside the body, injectable) insulin.
Do you see age specific B cell activation in your research?
Normally people think of type 1 diabetes as childhood diabetes, but there is now data that supports the idea that there are two types of endotypes in type 1 diabetes: those that develop it in a young age, for example less than 10 years, and those who develop it at a later age, even in adulthood. In our research, we believe that the activation of unwanted B cells is greater in young individuals who develop type 1 diabetes than in adults.
Has your research so far shown that type 1 diabetes is genetic?
There is certainly a genetic risk factor in the development of type 1 diabetes. However, what we see here at the Barbara Davis Center, and our colleagues have seen elsewhere, is that up to 75% of people who have recently diagnosed with type 1 diabetes do not actually have a family history of type 1 diabetes.
At the same time, there are a number of different genes that have been linked to the development of type 1 diabetes. Some of these genes are important in B cells and B cell development. We believe that if you have a single mutation in some of these genes, it alters the ability of these B cells to be properly deactivated by anergy, allowing these cells to activate and participate in disease.
In our research, we found that impaired B-cell anergy can occur in first-degree relatives who are not autoantibody positive or diagnosed with type 1 diabetes, demonstrating a likely genetic component of the disease. loss of B cell anergy.
What do you hope will be the next iteration of your research?
One of the goals we have at the Barbara Davis Center is to understand which subset of B cells is particularly important in the development of type 1 diabetes and what their exact function is. We recently received a grant to study the transcriptome and repertoire of autoreactive B cells at the single-cell level in newly diagnosed type 1 diabetics and in controls.
The goal is to take this information and hopefully develop more targeted therapies to specifically suppress the B cell subsets responsible for disease initiation to prevent or delay the development of type 1 diabetes.
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