How B cells fight the COVID-19 virus

Studies of antibody-producing B cells from patients who have recovered from COVID-19 reveal new cross-reactive antibodies and why some B cells are more effective in neutralizing the virus.

In the human body with COVID-19, the immune system B cell Engaged in a full-scale fight against the SARS-CoV-2 virus. However, some B cells do better than others. Scientists at MIT and Harvard’s Broad Institute of MIT and Harvard, Massachusetts General Hospital, California Institute of Technology, Brigham and Women’s Hospital, and other institutions are now explaining for the first time important features of B cells that are effective in neutralizing or inactivating. Did. SARS-CoV-2 virus and related coronavirus.

The team studied Blood sample From 14 individuals who recovered from COVID-19 and revealed a clear pattern of gene expression in B cells that produce antibodies that tightly bind and neutralize SARS-CoV-2. They also discovered a new antibody, BG10-19, that neutralizes the virus, a variant of concern, such as the one first identified in the United Kingdom and South Africa, and the coronavirus that caused the outbreak of SARS in 2003.

Survey results released today cellMay help scientists better understand why some people are not responding to existing COVID-19 vaccines and treatments, which is the first step towards improving vaccines and treatments.

“By studying patients with COVID-19 who have recovered from the virus, we learned a lot about the body’s defense mechanisms. Not all B cells are the same, and some are superantibody-producing cells. I found out. Design an antibody that can neutralize some coronaviruses. ” Director of the Center for Computational Integrated Biology at Mass General and Professor of Medicine at Harvard Medical School. “This study was the result of an amazing multicenter study involving caregivers, immunologists, computational biologists, and structural biologists.”

Better b cells

B cells or B lymphocytes play an important role in the body’s adaptive immune response. The day after a new virus infection, B cells produce antibodies that recognize the unique parts of the invading virus and tag it for destruction by other immune cells. Ultimately, some of these B cells are stored as “memory B cells,” helping the body launch attacks on the same virus more quickly in the future.

While other scientists have studied antibodies that bind strongly to SARS-CoV-2 and used that information to design vaccines and treatments, Xavier’s group has B cells that produce these strong antibodies. I wondered if there was anything unique in.

“The hope is to finally understand why some people have a stronger immune response to COVID-19 or existing vaccines,” said a new treatise, Broad researcher in Xavier’s lab. Co-lead author Johannes Xavier said. Researcher in Gastroenterology, Massachusetts General Hospital.

Scheid, along with other co-lead authors Christopher Barnes of the California Institute of Technology, Basak Eraslan of Broad and his colleagues, analyzed blood samples from 14 COVID-19 patients diagnosed in March 2020. The sample was from the COVID-19 biobank. This is a collaboration between Broad, Biogen and Mass General Brigam.

Researchers investigated the B cells in each patient and found more than 6,000 cells that bound to the SARS-CoV-2 virus. They narrowed down to 92 antibodies from the four individuals whose serum most strongly neutralized the virus and studied B cells that produce these antibodies.

B cells that most strongly responded to SARS-CoV-2 had unique patterns of gene expression, which were shared among different patients. The most strongly bound and neutralized B cells to the virus belonged to a population of cells called memory B cells and activated B cells. These B cells produced antibodies primarily known as immunoglobulin G (IgG), rather than other types of immunoglobulins.

“To understand where some of our current immune responses are missing, it’s important to have a map of what a successful B cell response will look like,” says Scheid. “That’s what we did here. We created portraits that could compare other immune responses.”

The researchers then characterized the B-cell response of immunosuppressed COVID-19 patients, and the B-cell response to the current COVID-19 vaccine was similar to that seen in the COVID-19 patients they studied. I want to find out if there is. It is ultimately how the immunological memory of vaccinated individuals differs from that of people who have recovered from COVID-19, and that immunosuppressed patients from COVID-19. It may help researchers understand how to protect well.

Antibody insights

When the research team examined the antibodies produced by the most potent B cells, one antibody, especially known as BG10-19, attracted the attention of researchers. BG10-19 not only neutralized all variants of the SARS-CoV-2 virus investigated, including those known as South African and British variants, but also caused the outbreak of SARS in 2003. It also neutralized the virus SARS-CoV.

In collaboration with structural biologists such as Christopher Barnes and Pamela Björkmann of the California Institute of Technology, researchers have shown how BG10-19 neutralizes SARS-CoV-2. BG10-19 attaches to regions on the virus that other antibodies also recognize, but the team found that it binds and anchors the virus in a closed conformation in a way not previously described. ..

The group plans to do further research on which coronavirus BG10-19 neutralizes and, if so, how. Virus Whether the antibody can escape and BG10-19 can be modified to enable it against a wider range of potentially harmful coronaviruses.

“The ability to bind so many different coronaviruses means that this antibody can be a good starting point for designing new ones. antibody It can be widely used in the future. ”