A NOVEL CHIMERIC ANTIBODY DASS IN CARTILAGINOUS FISH - IGM MAY NOT BETHE PRIMORDIAL IMMUNOGLOBULIN

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.