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Related Experiment Video

Updated: Aug 2, 2025

Generation of Recombinant Human IgG Monoclonal Antibodies from Immortalized Sorted B Cells
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Evolution of immunogenetic components encoding ultralong CDR H3.

Jeannine A Ott1, Christian Mitchell1, Morgan Sheppard1

  • 1Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.

Immunogenetics
|April 21, 2023
PubMed
Summary

Cattle and bison possess unique ultralong antibody gene segments, enabling diverse antigen binding. These specialized immunoglobulin (Ig) gene segments evolved in a common ancestor of the Bos and Bison genera approximately 5-10 million years ago.

Keywords:
AntibodyCattleDiversity segmentEvolutionIgH locusUltralong CDR H3

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Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches
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Area of Science:

  • Immunology
  • Genomics
  • Evolutionary Biology

Background:

  • Vertebrate antibody diversity arises from V, D, and J gene segments, creating variable CDR3 sequences.
  • Cattle exhibit fewer VDJ segments, necessitating alternative strategies for antibody diversity, such as ultralong-encoding IGHV and IGHD gene segments.
  • These ultralong segments generate elongated CDR H3 regions and unique paratope microdomains for broad antigen epitope binding.

Purpose of the Study:

  • To investigate the evolutionary timeline of ultralong-encoding immunoglobulin heavy variable (IGHV) and immunoglobulin heavy diversity (IGHD) gene segments in Bovidae species.
  • To determine when the genetic duplication responsible for the TTVHQ motif in ultralong IGHV segments emerged.

Main Methods:

  • Genome sequencing and analysis of twelve Bovidae species.
  • Identification of specific 8-bp duplications within IGHV segments.
  • mRNA analysis from bison spleen to assess the expression of ultralong CDR H3 antibody transcripts.

Main Results:

  • The 8-bp duplication encoding the TTVHQ motif in ultralong IGHV segments was found in six Bovid species within the Bos and Bison genera.
  • Ultralong-encoding IGHD gene segments were identified in the same species, excluding the domestic yak, and were confined to the Bos and Bison clade.
  • Bison spleen mRNA analysis revealed a rich repertoire of expressed ultralong CDR H3 antibody transcripts, indicating their use in host defense.

Conclusions:

  • The genetic duplication for ultralong IGHV segments and the emergence of ultralong IGHD segments likely occurred in a common ancestor of the Bos and Bison genera.
  • This evolutionary event is estimated to have happened 5-10 million years ago, providing a unique mechanism for antibody diversity in these lineages.