Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

Abstract

The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise. Additionally, these technologies also hold great promise for therapeutic antibody and biomarker discovery in a variety of settings

Proteomic Analysis of Pemphigus Autoantibodies Indicates a Larger, More Diverse, and More Dynamic Repertoire than Determined by B Cell Genetics

“…These data show that some of the memory B-cell/plasmablast clonotypes identified by APD in this and previous studies do contribute to the serologic response, however, most of the B-cell clonotypes identified by APD contribute few if any circulating abs. This is consistent with data that most memory B-cells may not contribute significantly to the serologic response (Wine et al, 2015), and is consistent with data shown below that some anti-Dsg B-cell clonotypes detected by NGS at one time point may not produce ab at that same time point.…”

“…This finding is similar to what has been noted in the circulating ab clonotypes after tetanus toxoid vaccination in which a single clonotype can contribute as much as 10-15% of the antigen specific ab response and most clonotypes contribute very little (Lavinder et al, 2014; Wine et al, 2015). However, we also found that the highly producing B-cell clones vary at different time points (Figure 5B).…”

“…However, such genetic studies may not necessarily reflect the actual circulating autoabs. In fact, a recent review of serum antibodies pointed out that even after a century of immunology research, circulating serum ab clonotypes have been characterized minimally if at all (Wine et al, 2015). Since it is unclear whether genetic analysis of autoabs reflect the serum autoab repertoire, and because it is the circulating serum autoantibodies that cause disease, we characterized the circulating autoab repertoire in patients with pemphigus vulgaris (PV) and foliaceus (PF), two prototypical tissue-specific, autoab-mediated, autoimmune conditions in which the antigens are well defined as the epidermal cell adhesion molecules desmoglein (Dsg) 3 and Dsg1, respectively (Stanley and Amagai, 2006).…”

Omics Approaches for the Study of Adaptive Immunity to Staphylococcus aureus and the Selection of Vaccine Candidates

“…Focusing on the host immune defense, proteomics, especially when combined with next-generation sequencing [146], opens new avenues for the elucidation of the antibody- and T-cell repertoires [147,148]. This technology has not yet been applied to comprehensively map the T response to S. aureus .…”

“…Immunoproteomics is a sub-discipline of immunomics, which aims at studying the function and regulation of the immune system in its entirety using omics approaches [147,148,153,154,155]. Immunoproteomics builds on proteomics for the comprehensive analysis of the adaptive immune response.…”