A novel "chimeric" antibody class in cartilaginous fish: IgM may not be the primordial immunoglobulin.
Using a degenerate oligonucleotide primer specific for immunoglobulin (Ig) constant type 1 (C-1 set) domain genes, products were amplified by the reverse transcriptase-polymerase chain reaction from nurse shark spleen cDNA. The deduced protein sequence of one of these clones reveals a novel Ig class in cartilaginous fish. A complete mRNA could encode a mature protein bearing an amino-terminal variable (V) domain, followed by six C-1 set domains, and ending in a carboxy-terminal tail typical of secreted IgM, IgA, and the new antigen receptor (NAR). The two amino-terminal C domains are orthologous to IgX (or IgR), an Ig heavy (H) chain class in the skate, and the last four domains are homologous to the carboxy-terminal four domains of NAR. We designate this "chimeric" Ig class IgNARC for Ig new antigen receptor from cartilaginous 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 bands that hybridize with exon-specific probes varies with genomic DNA from individual sharks, suggestive of different numbers of IgNARC genes in different animals. A protein of approximately 95 kDa, which is likely to be the IgNARC H chain, is immunoprecipitated with both light chain-specific monoclonal antibodies and with antisera generated to a peptide comprising the IgNARC carboxy-terminal tail. We conclude that the arsenal of secreted antigen receptors in cartilaginous fish is greater than previously believed. In addition, our data cast doubt on the dogma that IgM is the primordial Ig isotype.
Greenberg
A S
AS
Department of Microbiology and Immunology, University of Miami, FL 33101, USA.
Hughes
A L
AL
Guo
J
J
Avila
D
D
McKinney
E C
EC
Flajnik
M F
MF
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002678:Chimera; D005803:Genes, Immunoglobulin / Q000276:immunology*; D008040:Genetic Linkage; D007127:Immunoglobulin Constant Regions / Q000235:genetics / Q000302:isolation & purification; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000302:isolation & purification; D007075:Immunoglobulin M / Q000737:chemistry / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000302:isolation & purification; D007136:Immunoglobulins / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D011946:Receptors, Antigen / Q000235:genetics / Q000302:isolation & purification; D012754:Sharks / Q000235:genetics* / Q000276:immunology*
D007127:Immunoglobulin Constant Regions; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D011946:Receptors, Antigen; C092388:nurse shark antigen receptor