A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG

A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG

^*Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-138), Miami, FL 33101; ^†Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, MD 21201; ^‡Basel Institute for Immunology, Basel 4005, Switzerland; ^§The Scripps Research Institute, La Jolla, CA 92037; and ^¶Moss Landing Marine Labs, Moss Landing, CA 95039

Edited by Michael Potter, National Institutes of Health, Bethesda, MD, and approved December 15, 2000 (received for review August 3, 2000)

Abstract

In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM_1gj, from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells (“germline-joined”). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H_1gj in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H_1gj chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM_1gj. Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

Footnotes

↵ ‖ To whom reprint requests should be addressed at: BRB 13-009, 655 West Baltimore Street, Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201. E-mail: MFlajnik{at}som.umaryland.edu.
This paper was submitted directly (Track II) to the PNAS office.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database [accession nos. AF327520 (IgM_1gj) and AF327519 (TdT)].
↵ ** IgM_1gj is so-named because it is related to conventional IgM; 1 refers to the 1st IgM gene expressed in ontogeny and expression in primary lymphoid tissue; and gj signifies that the variable gene is germline joined.
Abbreviations:

TCR,

T cell receptor;

MHC,

major histocompatibility complex;

CDR,

complementarity-determining region