Abstract

Improving understanding of the bovine adaptive immune response would equip researchers to more efficiently design interventions against pathogens that impact upon food security and animal welfare. There are features of the bovine antibody response that differ substantially from other mammalian species, including the best understood models in the human and mouse. These include the ability to generate a functionally diverse immunoglobulin response despite having a fraction of the germline gene diversity that underpins this process in humans and mice, and the unique structure of a subset of immunoglobulins with “ultralong” HCDR3 domains, which are of significant interest with respect to potential therapeutics, including against human pathogens. However, a more detailed understanding of the B cell response and the production of an effective antibody response in the bovine is currently hampered by the lack of reagents for the B cell lineage. In this article we outline the current state of knowledge and capabilities with regard to B cell and antibody responses in cattle, highlight resource gaps, and summarize recent advances that have the potential to fundamentally advance our understanding of this process in the bovine host.

Highlights

  • Frontiers in ImmunologyThere are features of the bovine antibody response that differ substantially from other mammalian species, including the best understood models in the human and mouse

  • The molecular basis of how antibody repertoires are generated is broadly similar between mammalian species

  • Our understanding of the bovine B cell and antibody response has advanced significantly in recent years, with genomic and experimental data resolving the unique manner in which the cow generates immunoglobulin diversity from a restricted germline VH repertoire

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Summary

Frontiers in Immunology

There are features of the bovine antibody response that differ substantially from other mammalian species, including the best understood models in the human and mouse. These include the ability to generate a functionally diverse immunoglobulin response despite having a fraction of the germline gene diversity that underpins this process in humans and mice, and the unique structure of a subset of immunoglobulins with “ultralong” HCDR3 domains, which are of significant interest with respect to potential therapeutics, including against human pathogens. In this article we outline the current state of knowledge and capabilities with regard to B cell and antibody responses in cattle, highlight resource gaps, and summarize recent advances that have the potential to fundamentally advance our understanding of this process in the bovine host

INTRODUCTION
ADVANCES IN CLONAL ANALYSES OF ANTIBODY RESPONSES IN OUTBRED SPECIES
REAGENTS FOR STUDYING B CELL RESPONSES IN CATTLE
GENOMIC ORGANIZATION OF IMMUNOGLOBULIN GENES IN THE COW AND DIVERSITY GENERATION
IN VITRO CULTURE OF ACTIVATED B CELLS
IMMORTALISATION OF B CELLS BY INFECTION WITH THEILERIA ANNULATA
IMMUNOGLOBULIN GENES EXPRESSED BY SINGLE B CELLS
SUMMARY AND CONCLUSIONS
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