APR 09, 2018 12:55 PM PDT

Unique Molecular Interactions Dictate B Cell Tolerance

WRITTEN BY: Kara Marker

An important cellular reaction mediates part of the immune system responsible for tolerance. Without tolerance, the immune system would target harmless “self” cells like it does in the case of autoimmune disease. From the Medical University of South Carolina, scientists uncover a new checkpoint involved in regulating B cells.

Representation of a B cell.

Tolerance in the immune system is vital for preventing autoimmune reactions against harmless substances that the immune accidentally recognizes as dangerous. There are more than 80 types of autoimmune diseases, and there are 24 million people affected by autoimmune diseases in the United States. Women are more likely than men to have an autoimmune disease.

Researchers from the present study have historically been focused on cellular mechanisms that regulate the adaptive, or specific immune response, and the innate, or non-specific immune response. They are especially interested in uncovering the role of the immune system in cancer and autoimmune disease. Two proteins are especially important to their studies: TGF-beta and GARP.

TGF-beta is a “master cytokine” that regulates inflammation and tolerance. Recent research described GARP binding TGF-beta on regulatory T cells and platelets, affecting their activity. But the present study is the first to describe how GARP and TGF-beta binding affects activity of peripheral B cells in the context of immune tolerance.

Researchers found that when B cells are activated, GARP is expressed, indicating it might be a potential checkpoint for B cell tolerance. They used two preclinical models to understand more about the effect of GARP, one with GARP overexpressed and one with GARP underexpressed.

When GARP was overexpressed, B cells proliferated and activated less, and underexpression of GARP led to the development of spontaneous lupus-like disease, an autoimmune disease. Researchers also compared GARP expression across different populations of B cells.

"If you look at GARP expression on B cells, usually it's only expressed on activated B cells in the periphery,” Zihai Li, MD, PhD. “But in the gut, it looks like, even in the steady state, GARP is expressed.”

Why the gut? Researchers explain that because it is exposed to the environment, tissues of the gastrointestinal (GI) tract have to keep track of bacteria, viruses, food antigens, and self-antigens. B cells in an area called “Peyer’s patches” have an increased level of GARP expression. And without GARP, B cell proliferation and activation increased. Researchers theorize that the interaction between GARP and TGF-beta is most important in the gut because B cells need to be able to tolerate harmless food and self antigens.

"Our work started from a very simple question: What does GARP do? But as you can see, we have now shown that this pathway is important for autoimmune disease in a mouse model,” Li said. “And our work in humans suggests that this pathway is really relevant to human health.”

The present study was published in the journal JCI Insight.

Sources: Current Opinion in Immunology, Medical University of South Carolina

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
MAY 07, 2018
Immunology
MAY 07, 2018
Breast Milk: An Important Source of Protective Immune Cells
For the first time, scientists have identified innate lymphoid cells (ILCs) among the arsenal of protective cells transferred to newborn babies via breast...
MAY 24, 2018
Immunology
MAY 24, 2018
The Link Between Tuberculosis and Parkinson Disease
There might be a link between Tuberculosis (TB) and Parkinson’s according to a study published in The EMBO Journal. This link is related to the mecha...
JUL 23, 2018
Immunology
JUL 23, 2018
Obesity Associated Inflammation Leads to Chronic Health Issues
Inflammation caused by harmful oxidized lipids increases in individuals with obesity and may contribute to chronic disease development....
JUL 25, 2018
Immunology
JUL 25, 2018
T Cell Response to Ebola Virus Proteins
Killer T cells of Ebola survivors respond better to nucleoproteins, not glycoproteins, potentially influencing Ebola vaccine development....
AUG 04, 2018
Microbiology
AUG 04, 2018
The Viral Link to Irritable Bowel Disease
We now know of the importance of the microbiome, but most of the research focus has been on bacteria....
AUG 28, 2018
Cell & Molecular Biology
AUG 28, 2018
Finding the Source of a Common Immune Cell
Neutrophils are a highly abundant type of immune cell, outnumbering every other kind that runs through the bloodstream....
Loading Comments...