Memory B cells play a critical role in providing long-term immunity after vaccination or infection. Researchers at the University of Alabama at Birmingham identified a subset of FcRL5+ T-bet+ hemagglutinin-specific memory B cells that predicts long-lived antibody responses to influenza vaccination in humans. These effector memory B cells appear to be poised for a rapid serum antibody response upon secondary challenge one year later. The study may help identify a new way to predict influenza vaccine durability that would give an answer in days, rather than weeks or months. The research also found that human tonsil-derived FcRL5+ T-bet+ memory B cells differentiate more rapidly into antibody-secreting cells in vitro than FcRL5neg T-betneg hemagglutinin-specific memory B cells.
New Subset of Memory B Cells can Predict Long-term Antibody Responses to Influenza Vaccine
In a recent study published in the journal Immunity, researchers discovered a unique subset of memory B cells that can predict long-lived antibody responses to influenza vaccination in humans. The researchers, including Anoma Nellore, M.D. and Fran Lund, Ph.D., from the University of Alabama at Birmingham and Emory University, respectively, discovered that these effector memory B cells can rapidly produce serum antibodies upon secondary challenge one year later.
The researchers identified this novel subset by the presence of FcRL5 receptor protein on the cell surface, which acts as a surrogate marker for positive expression of the T-bet transcription factor inside the cells. They found that FcRL5+ T-bet+ memory B cells can be detected seven days after immunization, and the presence of these cells correlates with vaccine antibody responses months later.
Transcriptional and epigenetic profiling revealed that the cells in this subset differ from all previously described memory B cell subsets. As a result, these cells may represent an early, easily monitored cellular compartment that can predict the development of a long-lived antibody response to vaccines.
Pharmaceutical companies must test and manufacture new annual influenza vaccines months in advance of the winter flu season, and currently, an educated guess is made as to which flu strain will be circulating the next winter. However, the researchers suggest that this new subset of memory B cells may provide a new way to predict influenza vaccine durability, allowing for quicker testing of flu vaccines closer to flu season. This could potentially give us a better shot at predicting the right flu strain for the new annual vaccine.
In conclusion, this discovery could be a boon to the development of a more effective yearly influenza vaccine. By monitoring this new subset of memory B cells, researchers could predict the efficacy of a vaccine in days rather than weeks or months, potentially leading to a more accurate and effective vaccine that better protects us against the flu.
New Study Shows How Memory B Cells Respond to Flu Vaccines
Seasonal flu is a major cause of mortality worldwide, with estimates of 290,000 to 650,000 people dying from it each year, according to the World Health Organization. The global flu vaccine market was worth more than $5 billion in 2020. To better understand how vaccines work against the flu, researchers at the University of Alabama at Birmingham and Emory University conducted a study published in the journal Immunity.
The study revealed a unique subset of memory B cells that can predict long-lived antibody responses to influenza vaccination in humans. These effector memory B cells rapidly produce serum antibodies upon secondary challenge one year later.
Memory B cells play a critical role in providing long-term immunity after vaccination or infection. These cells can either produce new daughter cells or rapidly proliferate and differentiate into short-lived plasmablasts that produce antibodies. The latter are called “effector” memory B cells.
The researchers compared four types of B cells: naïve B cells, FcRL5+ T-bet+ hemagglutinin-specific memory B cells, FcRL5neg T-betneg hemagglutinin-specific memory B cells, and antibody-secreting B cells. They found that the FcRL5+ T-bet+ hemagglutinin-specific memory B cells were transcriptionally similar to effector-like memory cells, while the FcRL5neg T-betneg hemagglutinin-specific memory B cells exhibited stem-like central memory properties.
The researchers identified this novel subset by the presence of FcRL5 receptor protein on the cell surface, which acts as a surrogate marker for positive expression of the T-bet transcription factor inside the cells. They found that FcRL5+ T-bet+ memory B cells can be detected seven days after immunization, and the presence of these cells correlates with vaccine antibody responses months later.
The FcRL5+ T-bet+ hemagglutinin-specific memory B cells did not express the plasma cell commitment factor, but did express transcriptional, epigenetic and metabolic functional programs that poised these cells for antibody production. These included upregulated genes for energy-intensive metabolic processes and cellular stress responses.
“The best vaccines induce the formation of long-lived plasma cells and memory B cells,” said Fran Lund, Ph.D., the Charles H. McCauley Professor in the UAB Department of Microbiology and director of the Immunology Institute. “Plasma cells live in your bone marrow and make protective antibodies that can be found in your blood, while memory B cells live for many years in your lymph nodes and in tissues like your lungs. If plasma cells wane after vaccination, memory B cells become very important because these long-lived cells can rapidly respond to infection and can quickly begin making antibody.”
The researchers suggest that this new subset of memory B cells may provide a new way to predict influenza vaccine durability, allowing for quicker testing of flu vaccines closer to flu season. This could potentially lead to a more accurate and effective vaccine that better protects us against the flu.
Memory B Cells Rapidly Transition to Antibody-Secreting Cells after Vaccination
According to a study published in Immunity, researchers have identified a transcriptionally distinct subset of effector memory B cells that predict long-lived antibody responses to vaccination in humans. The researchers found that FcRL5+ T-bet+ hemagglutinin-specific memory B cells can be detected seven days after immunization and quickly differentiate into antibody-secreting cells, a sign of early transition to antibody-secreting cells.
Furthermore, the study found that human tonsil-derived FcRL5+ T-bet+ memory B cells differentiate more rapidly into antibody-secreting cells in vitro than FcRL5neg T-betneg hemagglutinin-specific memory B cells. The research was led by Fran Lund, Ph.D., and Anoma Nellore, M.D., of the University of Alabama at Birmingham and was funded by National Institutes of Health grants and the UAB Center for Clinical and Translational Science.
The study’s co-authors include researchers from UAB’s departments of Microbiology and Medicine, the institutes of Informatics and Immunology, and the Center for Clinical and Translational Science, as well as Emory University School of Medicine.
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