Abstract
A central feature of vertebrate immune systems is the ability to form antigen-specific immune memory in response to microbial challenge and so provide protection against future infection. In conflict with this process is the ability that many viruses have to mutate their antigens to escape infection- or vaccine-induced antibody memory responses. Mutable viruses such as dengue virus, influenza virus and of course coronavirus have a major global health impact, exacerbated by this ability to evade immune responses through mutation. There have been several outstanding recent studies on B-cell memory that also shed light on the potential and limitations of antibody memory to protect against viral antigen variation, and so promise to inform new strategies for vaccine design. For the purposes of this review, the current understanding of the different memory B-cell (MBC) populations, and their potential to recognize mutant antigens, will be described prior to some examples from antibody responses against the highly mutable RNA based flaviviruses, influenza virus and SARS-CoV-2.
Highlights
A central feature of vertebrate immune systems is the ability to form antigen-specific immune memory in response to microbial challenge and so provide protection against future infection
This study shows that most memory B-cell (MBC) produced later in the germinal centre (GC) response have still not increased levels of somatic hypermutation (SHM) or antigen affinity, or proliferated significantly compared to plasma cells produced at the same time
Whilst some MBC re-enter the GC in response to a variant antigen the bulk of the MBC response is currently thought to involve immediate differentiation into antibody-forming cells (AFCs), the important advantage being a more rapid humoral antibody response to viral variants compared to a naïve response
Summary
The development of immune memory is a dynamic process involving the formation over time of memory B- and T-cell populations at different sites in the body. The specificities analyzed, were to widely different antigens, suggesting this type of interaction might occur rarely between more related epitope variants It is perhaps the case, that antibodies can bind multiple ligands in different ways, by being flexible and perhaps polyreactive, by having hydrophobic binding sites or by fortuitously having particular high strength interactions available; the chance of all such properties being increased in a more diverse memory pool that has not been selected on the basis of high affinity to the priming antigen. Thought to be a least in part a viral immune evasion strategy [51,52], it is the case that the AFC population is far less clonally diverse than the MBC population, perhaps making the AFC response more vulnerable to flipping into immunodominance during the complex dynamics and inter-clonal competition of a developing antibody response
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