A fuzzy response from memory B cells can protect against mutant viruses

Specialised memory cells found in our immune system play an important role in our ability to fight virus mutations such as those produced by the SARS-CoV2 virus, according to research at the University of Birmingham.

So-called virus escape mutants are variants of a virus which are typically produced when the body’s immune system is weak. The immune system can control the virus, but cannot prevent the mutated viruses from spreading.

A person with a normal immune response is able to suppress these mutants. The mechanisms by which this happens, however, are poorly understood.

A team at the University of Birmingham discovered an important role played by memory B cells. These work alongside the regular B cells which learn to produce highly specific antibodies in response to an infection. The results are published in Nature Communications.

Memory B cells work alongside these virus-neutralising antibodies, but their function has remained a puzzle. That’s because, while antibodies are highly specific to a target pathogen, memory B cells make antibodies that bind in a fuzzy and non-specific way.

The researchers found the reason for this lack of specificity was that memory B cells are interacting with other white blood cells, called phagocytes which work to suppress pathogens by engulfing them. The memory B cells work alongside phagocytes to continuously screen for mutant virus variants.

Because their function is not specialised, when they discover an antigen, they can kick-start a protective antibody response. This enables them to generate an early defence mechanism against virus escape variants during an ongoing infection.

The mechanism may protect us from SARS-CoV2 variants which emerge during an on-going Covid-19 infection and also seems to protect HIV patients from being overcome by virus mutant variants over many years.

Professor Kai-Michael Toellner, in the Institute of Immunology and Immunotherapy at the University of Birmingham, explains: “These findings enable us to better understand how people are protected in long term virus infections, such as HIV. It represents a major shift in how we think about immune memory, which may affect how we understand virus infection, and immune deficient patients – as well as the development of new vaccines.”

The research was funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council, both part of UK Research and Innovation.