Abstract

The generation of high affinity antibodies is a crucial aspect of immunity induced by vaccination or infection. Investigation into the B cells that produce these antibodies grants key insights into the effectiveness of novel immunogens to induce a lasting protective response against endemic or pandemic pathogens, such as influenza viruses, human immunodeficiency virus, or severe acute respiratory syndrome coronavirus-2. However, humoral immunity has largely been studied at the serological level, limiting our knowledge on the specificity and function of B cells recruited to respond to pathogens. In this review, we cover a number of recent innovations in the field that have increased our ability to connect B cell function to the B cell repertoire and antigen specificity. Moreover, we will highlight recent advances in the development of both ex vivo and in vivo models to study human B cell responses. Together, the technologies highlighted in this review can be used to help design and validate new vaccine designs and platforms.

Highlights

  • The humoral arm of the immune system plays a key role in vaccine-mediated immunity through the production of protective high-affinity neutralizing and non-neutralizing antibodies against diverse pathogens [1]

  • The novel techniques and innovations discussed in this review have great potential to deepen our understanding of B cell biology at an unprecedented pace

  • Taking fine needle aspirates at multiple timepoints, one can monitor for germinal center induction and affinity maturation in the lymph nodes or for new bone marrow immigrants and their continued survival over time [12,13,14]

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Summary

Introduction

The humoral arm of the immune system plays a key role in vaccine-mediated immunity through the production of protective high-affinity neutralizing and non-neutralizing antibodies against diverse pathogens [1]. The antigen reactivity and binding affinity of serum antibodies generated in response to vaccination or infection has been studied for decades using techniques such as enzyme-linked immunosorbent assays (ELISAs) or surface plasmon resonance (SPR), in addition to neutralization experiments to test the protectiveness of polyclonal sera against pathogens. These techniques, fail to provide information about the B cell clones involved in the immune response or the phenotypes of B cells recruited into the response. We will discuss the emerging technologies and techniques to investigate B cell specificity and function and how these new approaches can provide critical insight into B cell biology in the context of infection, vaccination, and autoimmunity

Connecting Antigen Specificity to B Cell Heterogeneity
Connecting B Cell Repertoires to Serum Antibody Specificities
Animal Models to Study the Humoral Immune System
Ex Vivo Models to Study the Human Humoral Immune System
Tracking B Cell Function In Vivo
Conclusions
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