Memory B cell diversity: insights for optimized vaccine design

• Published in: Trends in immunology 2022-05, Vol.43 (5), p.343-354
• Main Authors: McGrath, Joshua J.C., Li, Lei, Wilson, Patrick C.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Antibodies, Viral; Antigenic determinants; Antigens; B-Lymphocytes; Biomarkers; Cell surface; Coronaviruses; COVID-19; Design optimization; Enzymes; Genotype & phenotype; Humans; Immune imprinting; Immunologic Memory; Immunological memory; Influenza; Logos; Lymphocytes; Lymphocytes B; Mammals; Memory B Cells; Memory cells; Metabolism; Opinion; Pathogens; Phosphorylation; Population; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Surface markers; Vaccination; Vaccines; Viruses
• ISSN: 1471-4906; 1471-4981
• DOI: 10.1016/j.it.2022.03.005

The overarching logos of mammalian memory B cells (MBCs) is to cache the potential for enhanced antibody production upon secondary exposure to cognate antigenic determinants. However, substantial phenotypic diversity has been identified across MBCs, hinting at the existence of unique origins or subfunctions within this compartment. Herein, we discuss recent advancements in human circulatory MBC subphenotyping as driven by high-throughput cell surface marker analysis and other approaches, as well as speculated and substantiated subfunctions. With this in mind, we hypothesize that the relative induction of specific circulatory MBC subsets might be used as a biomarker for optimally durable vaccines and inform vaccination strategies to subvert antigenic imprinting in the context of highly mutable pathogens such as influenza virus or SARS-CoV-2. We hypothesize that circulatory memory B cell (MBC) subphenotypes with specific origins/subfunctions may correlate with the efficacy/durability of existing vaccines and therein may be useful biomarkers for vaccine candidate efficacy/durability in preclinical/clinical studies.We further speculate that investigating the manner in which antigen-specific MBCs are distributed across subclusters may provide insight into the optimal design of influenza virus/coronaviral vaccines that could subvert antigenic imprinting.Recent high-throughput proteomic screening and other techniques have helped refine our understanding of circulating MBC subphenotypes; CD45RB expression identifies a naïve-proximal, apparent ‘early’ population of CD27- MBCs.CD95 expression identifies a subset of naïve-distal, ‘advanced’ CD45RB+CD27+CD73+ MBCs and may contribute to plasmablast differentiation in response to soluble CD95L.Nonclassical MBC-like cells (CD19hiCD11c+CD21loCD27+/–CXCR3+/–T-bet+) are T cell-dependent, of germinal center-independent origin, seed secondary germinal centers, and develop into antibody-secreting cells during recall responses.