Blevins and Team Publish Exciting Research on Dioxin-like Compounds Effects on the Human B Cell and Immune Response

October 12, 2021

IIT-affiliated faculty member, Dr. Lance Blevins, along with colleagues, Dr. Norbert Kaminski, Dr. Jiajun Zhou, and Robert Crawford, are working on exciting research on dioxin-like compounds effects on the human B cell and its natural immune response properties. Dr. Blevins’ research since graduate school has typically focused on regulation of the adaptive immune response, particularly how dioxins modulate the immune response, especially in the human B cell. Dr. Blevins joined the Kaminski laboratory as a postdoctoral mentee in 2016 and then joined the IIT as an assistant professor earlier this year. Dr. Kaminski has been studying dioxins and their relation to B cells for several decades. Together, Drs. Kaminski and Blevins are now studying primary human B cells that they have isolated from the blood and recently published a ground-breaking paper in the journal Frontiers in Immunology, “Identification of a Sensitive Human Immunological Target of Aryl Hydrocarbon Receptor Activation: CD5+ Innate-Like B Cells.”  

“Of all the different cell types that make up the immune system, the B cell appears to be the most sensitive cell type within that system, especially with respect to affecting its function,” commented Dr. Blevins. The B cell contributes to immunity in the body by producing antibodies. Dioxin-like compounds can interfere with the production of these antibodies which has led to Dr. Blevins current research focus – how this specific subset of B cells (innate-like B cells) function when exposed to dioxins. Innate-like B cells are very similar to innate immune cells in that they are the body’s frontline defense against pathogens and produce natural antibodies. Innate-like B cells also help to regulate the immune response in the body. 

One of the more interesting findings from Dr. Blevins’ research is that dioxin seems to be taking advantage of innate-like B cells regulatory capabilities in order to suppress the immune response. PD-1, a protein widely studied in the context of cancer, is a receptor that works like an on/off switch for immune cells. “We actually found in this study that dioxin’s appeared to have the capability of causing these innate-like B cells to artificially upregulate this protein, PD-1, on their surface, making them more sensitive to being turned off, to flipping that light switch and affecting immunity,” said Dr. Blevins.  

“This is one of the first times this protein, PD-1, has actually been shown to be involved in a mechanism of immune toxicity where a chemical is causing a change in the immune system. Just like cancer cells can flip that switch with PD-1 to turn off the immune system and to evade it, now we are also showing that chemicals can make these innate-like B cells more sensitive to having that switch flipped against immunity as well,” commented Dr. Kaminski.  

Natural antibodies are very important early in life before the immune system is developed, and then as humans age, the immune system begins to wane and people become more sensitive to pathogens. If people are then exposed to dioxin-like compounds, it may be of greatest consequence to the very young and the very old, whose immune systems are at their most fragile state. “This research has been very relevant to our Superfund Program efforts in understanding the effects of dioxins around the Tittabawassee and Saginaw River Valley area where very concentrations of these contaminants have been found.” 

Dr. Blevins’ research has looked into a subset of B cell that has been previously under explored. “Starting to unravel this mystery of how AhR, which is the pertinent protein in relation to dioxin contamination, may actually be mediating some of these effects in the B cell that Dr. Kaminski’s lab has been studying for twenty plus years has been really gratifying and exciting,” Dr. Blevins commented. He is looking to continue this vein of research by drilling down even further into the innate-like B cell subsets, to focus on an even narrower niche of cells that seem to contain most of the regulatory capabilities within the cell pool. Dr. Blevins will continue to delve deeper into how these dioxin like compounds are actually mediating the decrease in the antibody response within these specific cell populations.