Abstract
Humoral immunity is key to protection for nearly all licensed vaccines. Yet, the design of vaccines has been more difficult for some of our most deadly killers (e.g. HIV, influenza, Dengue virus, etc.), likely due to our incomplete understanding of the precise immunological mechanisms associated with protection. Humoral immunity is governed both by B-cells and their bi-functional secreted antibodies, all of which have a unique capacity to evolve during an immune response. Current OMIC technologies capture individual features of the humoral immune response, providing a glimpse into humoral components (Fab/Fc/B-cell-omic), but fail to provide a wholistic view of the humoral response as a collective functional arm. Here, we dissect current OMIC strategies reviewing experimental and computational approaches, that if integrated could provide a true systems-level view of the humoral immune response.
Highlights
Genomics, transcriptomics, proteomics, metabolomics, and so on each provide high-dimensional molecular insights into biological processes both at the intracellular and extracellular level
The immune system includes a diverse constellation of cell types that must work together, combining innate and adaptive immune recognition and function, that synergize to mount an effective defense against pathogens
B-cells represent a unique OMIC challenge due to the diversity of both the cellular and secreted factors that collectively evolve to respond to disease
Summary
Transcriptomics, proteomics, metabolomics, and so on each provide high-dimensional molecular insights into biological processes both at the intracellular and extracellular level. Antibodies – the immune system’s complex weapon Unlike other molecules in the immune system, antibodies are unique moieties comprising two distinct functional domains: 1) the antigen-binding domain (Fab) conferring antigen-specificity, and 2) the constant fragment crystallizable (Fc) domain providing instructions to direct immune system functionality (Figure 1a) Both domains evolve rapidly during an immune response to improve antigen-recognition and ensure that all antibodyopsonized material is eliminated appropriately via the immune system. DNA segments for the Fc domain are eliminated to select distinct Fc isotypes/subclasses each with distinct shapes, flexibility and unique functional activities depending on the affinity and range of Fc-receptor/complement binding capacities (class switch recombination (CSR)) [7] Together, these genomic evolutionary processes of BCR evolution are unique www.sciencedirect.com
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