Four primordial immunoglobulin light chain isotypes, including λ and κ, identified in the most primitive living jawed vertebrates

Authors

  • Michael F. Criscitiello,

    1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, USA
    Search for more papers by this author
  • Martin F. Flajnik

    Corresponding author
    1. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, USA
    2. National Aquarium at Baltimore, Baltimore, USA
    • Department of Microbiology and Immunology, University of Maryland School of Medicine, 660 West Redwood Street, Howard Hall Suite 324, Baltimore, MD 21201, USA, Fax: +1-410-706-2129
    Search for more papers by this author

Abstract

The discovery of a fourth immunoglobulin (Ig) light (L) chain isotype in sharks has revealed the origins and natural history of all vertebrate L chains. Phylogenetic comparisons have established orthology between this new shark L chain and the unique Xenopus L chain isotype σ. More importantly, inclusion of this new L chain family in phylogenetic analyses showed that all vertebrate L chains can be categorized into four ancestral clans originating prior to the emergence of cartilaginous fish: one restricted to elasmobranchs (σ-cart/type I), one found in all cold-blooded vertebrates (σ/teleost type 2/elasmobranch type IV), one in all groups except bony fish (λ/elasmobranch type II), and one in all groups except birds (κ/elasmobranch type III/teleost type 1 and 3). All four of these primordial L chain isotypes (σ, σ-cart, λ and κ) have maintained separate V region identities since their emergence at least 450 million years ago, suggestive of an ancient physiological distinction of the L chains. We suggest that, based upon unique, discrete sizes of complementarity determining regions 1 and 2 and other features of the V region sequences, the different L chain isotypes arose to provide different functional conformations in the Ig binding site when they pair with heavy chains.

Ancillary