BOSTON – Until recently, B cells – present in the blood stream – were mainly thought to produce antibodies and present antigens to help with the immune response to pathogens. A research team at the Vaccine and Immunotherapy Center (VIC) at Massachusetts General Hospital (MGH) led by Ruxandra Sîrbulescu PhD, and Mark Poznansky, MD, PhD, is exploring the novel protective roles that B cells may play in the context of injury. The group previously observed that mature B cells purified from the blood or spleen can greatly accelerate wound healing in the skin and even protect the brain after injury in mice.
In a follow-up study published in the FASEB Journal– published by Federation of American Societies for Experimental Biology, the collaborative team elucidated a novel mechanism, they term pligodraxis (from the Greek pligí meaning wound, and drási meaning action), by which a subset of B cells introduced into a site of tissue injury undergo specific changes in response to the injured environment. Within one to two days after application into an injured site, these therapeutic B cells release a complex mix of specific pro- and anti-inflammatory molecules, which can in turn affect molecular processes in the surrounding cells, and ultimately facilitate healing.
“This is one example of many in biological research where it is beneficial to keep an open mind about what certain cell types can do or not,” says Sîrbulescu, lead author of the study and investigator at VIC. “ Had we not looked at B cells in this unconventional context we would have missed their ability to respond in such a complex way and interact with many different cell types in their environment to faciliate healing.”
Perhaps most surprisingly, these changes in B cell function occur via signaling molecules and pathways that are usually critically involved in responses to infection, indicating a useful repurposing of the existing tools in the cells’ repertoire in the context of sterile injury. The result is a reduction in the expression of inflammation-associated proteins, as well as an increase in factors associated with proliferation, remodeling and protection from oxidative stress. These findings provide a first mechanistic understanding of the complex ways in which B cells can modulate local microenvironments to support tissue repair following injury.
“These results are very exciting from the perspective of our translational medical research center, which sets as its core mission to accelerate the process by which discoveries are translated into new immunotherapies to address human disease in the clinic,” says Poznansky, director of the VIC at MGH and professor of Medicine at Harvard Medical School. “This particular discovery opens the way towards B cell immunotherapy for a diverse range of injury settings, from diabetic foot ulcers to traumatic brain injury.”
Sirbulescu and Poznansky work in collaboration with study co-authors Akshay Mamidi, Vaccine and Immunotherapy Center; Claire Shu-Yi Chan,MBBS; Gina Jin, BS,Vaccine and Immunotherapy Center; Myriam Boukhali, BS, Cancer Center, Massachusetts General Hospital; Don Sobell, BS,Vaccine and Immunotherapy Center, Iulian Ilieş PhD, North Eastern University; Joon Yong Chung, Pediatric Neuroscience Center, Massachusetts General Hospital; Wilhelm Haas PhD Cancer Center; Massachusetts General Hospital, Michael J. Whalen, MD, Pediatric Neuroscience Center, Massachusetts General Hospital; Ann E. Sluder, PhD, Vaccine and Immunotherapy Center.
About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2021, Mass General was named #5 in the U.S. News & World Report list of "America’s Best Hospitals."
FASEB is composed of 30 societies with more than 130,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB’s mission is to advance health and well-being by promoting research and education in biological and biomedical sciences through collaborative advocacy and service to member societies and their members. Visit faseb.org for more information.
The FASEB Journal
B cells support the repair of injured tissues by adopting MyD88-dependent regulatory functions and phenotype
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