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Identification of Mouse and Human Antibody Repertoires by Next-Generation Sequencing
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Shark IgW C region diversification through RNA processing and isotype switching.

Cecilia Zhang1, Louis Du Pasquier, Ellen Hsu

  • 1Department of Physiology and Pharmacology, State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA.

Journal of Immunology (Baltimore, Md. : 1950)
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Sharks possess a unique adaptive immune system with immunoglobulin (Ig) miniloci. This study reveals complex C region diversification pathways for IgW, enhancing effector function diversity in cartilaginous fishes.

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Area of Science:

  • Immunology
  • Evolutionary Biology
  • Marine Biology

Background:

  • Sharks and skates are early vertebrates with adaptive immunity.
  • Shark B cells express Immunoglobulin M (IgM) and Immunoglobulin W (IgW).
  • Ig genes in sharks are organized into autonomous miniloci.

Purpose of the Study:

  • To characterize nurse shark IgW heavy chain (H chain) miniloci.
  • To investigate the mechanisms of IgW C region diversification.
  • To understand the evolution of adaptive immunity in cartilaginous fishes.

Main Methods:

  • Characterization of eight distinct IgW H chain miniloci.
  • Analysis of gene segments (VH, D, JH) and C domain exons.
  • Assessment of gene rearrangement capability and amino acid sequences.
  • Investigation of isotype switching between IgW and IgM C regions.

Main Results:

  • Identified eight functional IgW H chain miniloci in nurse sharks.
  • Each minilocus contains VH, D, JH segments and multiple C domain exons.
  • Discovered gene clusters capable of generating at least six secreted IgW isoforms.
  • Demonstrated isotype switching occurs between IgW miniloci and to IgM C regions.

Conclusions:

  • Shark IgW H chain gene organization is complex, involving numerous miniloci.
  • Multiple mechanisms, including DNA-level switching and RNA processing, diversify IgW C regions.
  • These findings highlight unique evolutionary pathways for adaptive immunity and effector function diversity in cartilaginous fishes.