Scientists are uncovering new insights into B cells, which are immune cells long recognized for their role in producing antibodies.
A review by Oregon Health & Science University researchers published this week in Nature Reviews Immunology, reveals that B cells do much more — they work directly at areas of inflammation, where they become long-lasting cells that stay in the body. These cells can affect how diseases progress and how the body responds to treatments.
“We're focusing on the cell and its function in the tissue and tumor microenvironment, which has kind of been ignored for a long time,” said Joshua Moreau, Ph.D., assistant professor in the Division of Oncological Sciences, Department of Dermatology, Department of Cell, Developmental and Cancer Biology and a member of OHSU Knight Cancer Institute’s Cancer Early Detection Advanced Research Center, or CEDAR.
Moreau’s lab studies B cell responses in the tumor microenvironment. He is corresponding author on the review, along with Lauren Rodda, Ph.D., assistant professor of molecular microbiology and immunology in the OHSU School of Medicine.
Researchers now understand that B cells do not just operate in secondary lymphoid organs, such as lymph nodes, but are also active in non-lymphoid tissues, including those affected by infections, inflammatory diseases and cancer. These cells play key roles in immune responses, forming specialized structures known as tertiary lymphoid structures, which help coordinate local immune defenses.
“We felt like it was an important time to take a pause and try to summarize literature around B cells in non-lymphoid tissues,” said Rodda, whose lab studies lung B cell responses to respiratory infections. “Only in the last five to 10 years has it been appreciated that B cells can function and play important roles outside of the blood, spleen and lymph nodes.”
Recent advances in technology have allowed researchers to better understand how B cells work in our body. Studies show that B cells are attracted to areas in the body that are inflamed. Once there, they change into different types of cells that help fight off infections. Some of these B cells turn into memory cells, which stay in the body and help protect us from getting sick again in the future.
“The dogma for 50 or more years has been that B cells function in the spleen, in lymph nodes and in the blood,” Rodda said. “But blood also connects cells to lungs, liver, kidney, skin and the female reproductive tract. We need to understand what these cells are doing in these tissues.”
B cells play both helpful and harmful roles in the body. While they help fight infections and strengthen the immune system, certain types can also contribute to autoimmune diseases by causing inflammation. Some B cells, called regulatory B cells, release substances that help keep the immune system in balance. Understanding how B cells work in these different ways is important for creating treatments for diseases such as cancer and autoimmune disorders.
“That includes solid tumors where we now know there are actually B cells infiltrating these tumors,” Moreau said. “They have important ramifications for patient outcomes and response to immunotherapy or other treatments.”
Researchers are working to identify definitive markers for tissue-resident memory B cells and to map the molecular pathways that govern their activity. Gaining a deeper understanding of tertiary lymphoid structures formation and function could lead to new treatments that harness B cells to fight infections and cancers more effectively.
“We hope this review helps bring researchers together across different fields,” Rodda said. “Someone studying infection might learn something about tumors, and someone studying tumors might learn something about autoimmunity. We could be learning something about fundamental B cell biology that benefits all of us.”
These findings highlight the need to rethink traditional models of B cell function. Instead of viewing them mainly as antibody-producing cells, researchers now recognize them as versatile immune players that shape local immune responses in tissues. Future studies could pave the way for new immunotherapies that enhance B cell responses where they are needed most.
Postdoctoral researchers Abrar Samiea, Ph.D., and Rashi Yadav, Ph.D., from Moreau’s lab contributed to this study, along with Ph.D. student George Celis, B.S., from Rodda’s lab.
The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number T32GM142619, Melanoma Research Alliance, OHSU Molecular Microbiology and Immunology. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other sponsors.