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
OCT 12, 2021
Immunology
Major Landmark in a 100-Year Search for a Malaria Vaccine
OCT 12, 2021
Major Landmark in a 100-Year Search for a Malaria Vaccine
In one of the greatest global health milestones of our time, the World Health Organization has approved the widespread d ...
OCT 19, 2021
Cell & Molecular Biology
Mouse Fathers Passed Immunity Onto Offpsring After Infection
OCT 19, 2021
Mouse Fathers Passed Immunity Onto Offpsring After Infection
Parents pass their genes on to their children. But they can pass down other things too with epigenetic marks, chemical t ...
DEC 06, 2021
Microbiology
Sino Biological Launched Omicron Variant Research Reagents
DEC 06, 2021
Sino Biological Launched Omicron Variant Research Reagents
Sino Biological Newly Launched A Panel of Research Reagents for SARS-CoV-2 Omicron Variant (B.1.1.529) Beijing, China, D ...
DEC 11, 2021
Health & Medicine
Third Dose of Pfizer-BioNTech Vaccine Could Reduce Effects of Omicron
DEC 11, 2021
Third Dose of Pfizer-BioNTech Vaccine Could Reduce Effects of Omicron
Many mainstream media sources are reporting on a new press release from Pfizer that suggests that a third dose of the Pf ...
DEC 21, 2021
Immunology
Shark Immune Proteins as Pandemic 'Insurance'?
DEC 21, 2021
Shark Immune Proteins as Pandemic 'Insurance'?
Sharks are incredibly hardy creatures—they've survived in marine ecosystems, often unchallenged predators, for ...
JAN 07, 2022
Health & Medicine
Israel Approves Fourth Dose of COVID-19 Vaccine
JAN 07, 2022
Israel Approves Fourth Dose of COVID-19 Vaccine
While third doses are being approved for adults in countries worldwide, Israeli citizens are already receiving a fourth. ...
Loading Comments...