As. Greenberg et al., A NOVEL CHIMERIC ANTIBODY DASS IN CARTILAGINOUS FISH - IGM MAY NOT BETHE PRIMORDIAL IMMUNOGLOBULIN, European Journal of Immunology, 26(5), 1996, pp. 1123-1129
Using a degenerate oligonucleotide primer specific for immunoglobulin
(Ig) constant type 1 (C-1 set) domain genes, products were amplified b
y the reverse transcriptase-polymerase chain reaction from nurse shark
spleen cDNA. The deduced protein sequence of one of these clones reve
als a novel Ig class in cartilaginous fish. A complete mRNA could enco
de a mature protein bearing an amino-terminal variable (V) domain, fol
lowed by six C-1 set domains, and ending in a carboxy-terminal tail ty
pical of secreted IgM, IgA, and the new antigen receptor (NAR). The tw
o amino-terminal C domains are orthologous to IgX (or IgR), an Ig heav
y (H) chain class in the skate, and the last four domains are homologo
us to the carboxy-terminal four domains of NAR. We designate this ''ch
imeric'' Ig class IgNARC for Ig new antigen receptor from cartilaginou
s fish. Like NAR, but unlike shark IgM, IgNARC is encoded by very few
V and C genes which apparently are not closely linked. The number of b
ands that hybridize with exon-specific probes varies with genomic DNA
from individual sharks, suggestive of different numbers of IgNARC gene
s in different animals. A protein of approximately 95 kDa, which is li
kely to be the IgNARC H chain, is immunoprecipitated with both light c
hain-specific monoclonal antibodies and with antisera generated to a p
eptide comprising the IgNARC carboxy-terminal tail. We conclude that t
he arsenal of secreted antigen receptors in cartilaginous fish is grea
ter than previously believed. In addition, our data cast doubt on the
dogma that IgM is the primordial Ig isotype.