Immunoglobulin isotypes in Atlantic salmon, Salmo salar

Abstract

There are three major immunoglobulin (Ig) isotypes in salmonid fish: IgM, IgD and IgT, defined by the heavy chains μ, δ and τ, respectively. As a result of whole genome duplication in the ancestor of the salmonid fish family, Atlantic salmon (Salmo salar) possess two highly similar Ig heavy chain gene complexes (A and B), comprising two μ genes, two δ genes, three intact τ genes and five τ pseudogenes. The μA and μB genes correspond to two distinct sub-populations of serum IgM. The IgM-B sub-variant has a characteristic extra cysteine near the C-terminal part of the heavy chain and exhibits a higher degree of polymer disulfide cross-linking compared to IgM-A. The IgM-B:IgM-A ratio in serum is typically 60:40, but skewed ratios are also observed. The IgT isotype appears to be specialized to mucosal immune responses in salmonid fish. The concentration of IgT in serum is 100 to 1000 times lower than IgM. Secreted forms of IgD have been detected in rainbow trout, but not yet in Atlantic salmon.

Figure 1

Schematic overview of secreted and membrane anchored IgM and IgT of salmonid fish, compared with human IgM. Serum IgM is a tetramer in teleosts. In contrast to the IgM pentamer in mammals, the monomer units in teleost IgM are loosely linked by disulfide bonding, and the J chain is lacking. Membrane anchored IgM in teleosts is one domain shorter than in mammals as a result of a special splicing pattern which excludes the entire fourth constant domain. Salmonid IgT appears to be non-covalently bonded tetramers in mucus. The similarity between the first constant domains of IgM and IgT is relatively high (52%) in Atlantic salmon, whereas the remaining domains of the heavy chains are only 13%–24% similar [7].

Figure 2

(a) A monoclonal antibody (Mab4C10) raised against rainbow trout IgM reacts exclusively with IgM-A in Atlantic salmon, whereas in brown trout it reacts with IgM-B. A coomassie stained gel of reduced IgM-B (lane 1) and IgM-A (lane 2) from brown trout, and IgM-B (lane 3) and IgM-A (lane 4) from salmon is shown (the lanes are indicated below the gel), and the reactivity with Mab4C10 is indicated with arrows (b) Schematic overview of amino acid substitutions in μ sub-variants of Atlantic salmon and brown trout. A cysteine residue near the C-terminal part of μ4 is characteristic for the μB sub-variant in Atlantic salmon and brown trout (indicated with blue). Residues which are identical in salmon μA and brown trout μB are indicated with green. By in vitro mutagenesis and transfection experiments it was shown that a proline (indicated with an arrow) in μ3 is essential for binding of Mab4C10 [35].

Figure 3

Comparison of serum immunoglobulin (IgM) concentrations in different teleosts [40] compared to human (IgM + IgG + IgA). IgM is indicated with dark blue, IgG with light blue and IgA with red.