Johns Hopkins and four collaborating institutions have found an existence of a long-doubted “X-cell” a “rogue hybrid” immune system cell that may play a key role in the development of type 1 diabetes. They have published their findings in the journal Cell.
What did they Discover?
They report an unusual lymphocyte (type of white blood cell), formally known as a dual expressor, or DE, cell. Researcher Abdel-Rahim A. Hamad reports, “the cell we have identified is a hybrid between the two primary workhorses of the adaptive immune system, B lymphocytes and T lymphocytes” and that “our findings not only show that the X cell exists, but also that there is strong evidence for it being a major driver of the autoimmune response believed to cause type 1 diabetes.”
What is Unique about the Entity Discovered?
Hamad notes, “What is unique about the entity we found is that it can act as both a B cell and a T cell” and emphasized “This probably accentuates the autoimmune response because one lymphocyte is simultaneously performing the functions that normally require the concerted actions of two.”
Commentary on B and T Lymphocytes
B and T lymphocytes each possess distinctly different cell receptors—the B cell receptor, or BCR, and T cell receptor, or TCR, respectively—that work together to help identify and target antigens—the bacteria, viruses and other foreign invaders that trigger an immune response. Normally, this defense begins when the trespasser is engulfed by a white blood cell called an antigen presenting cell, or APC. The name arises from the fact that an antigenic protein from the ingested intruder is “presented” on the surface of the APC.
After this occurs, the APC travels to a part of the body, such as a lymph node, where immature B and T cells reside. A T cell with a TCR whose shape conforms to the presented antigen—akin to fitting a key into a lock-can latch on, triggering its maturation into either a helper or killer T cell.
Helper T cells then activate immature B cells whose BCRs also conform to the shape of the presented antigen to mature them into either plasma cells that produce antibodies to remove the foreign material from the body or memory cells that “remember” the antigen’s biochemistry for a faster response to future invasions.
Killer, or cytotoxic, T cells, on the other hand, directly attack the invaders to which they’ve been primed as a result of the immature T cell’s initial contact with the antigen.
However, when this process goes haywire with the B cells and T cells seeking out and attacking normal cells—the case of mistaken identity known as an autoimmune response—the results can be devastating.
More on Type 1 Diabetes
For type 1 diabetes, scientists have long believed that the immune system somehow becomes confused and sees insulin as a target. Therefore, the misguided cellular defense forces wage war on the beta cells in the pancreas that produce the hormone, drastically lowering the amount available and leading to the high blood sugar levels characteristic of diabetes.
What isn’t well understood is the mechanism that drives the assault against the beta cells. The DE cell identified by Hamad and his colleagues, and a unique protein that it produces, appear to be the key agents for at least one possible pathway.
“It is well accepted that insulin is seen as an antigen by the T cells and that this occurs when the hormone is bound to a site on the APC known as HLA-DQ8,” Hamad explains. “However, our experiments indicate that it is a weak binding and not likely to trigger the strong immune reaction that leads to type 1 diabetes.”
Instead, the findings from the new study show that when a second protein, one coded by the BCR present on the DE cell, is substituted for insulin, it binds so tightly that it can elicit a T cell response 10,000 times stronger.
These were conducted by Ruhong Zhou, PhD, and his team at IBM Thomas J. Watson Research Center.
The team looks to study that probable link in greater depth to confirm and more extensively define it. It is believed that the development of such knowledge could lead to the development of methods to screen individuals at risk for developing type 1 diabetes.