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GENETIC polymorphism of the structural genes encoding the class-specific (heavy) polypeptide chains of the immunoglobulin (Ig) molecules provides a useful set of markers for elucidating the arrangement and expression of these genes. On the basis of various antigenic, physiochemical and biological properties, the immunoglobulins of the mouse have been divided into eight distinct classes, IgM, IgD, IgA, IgG1, IgG2a, IgG2b, IgG3 and IgE, with a specific structural gene determining the heavy chain (H) for each class. Previous studies have documented the existence of a genetic polymorphism for five of these H-chain genes1–3, with all the genes being closely linked constituting a heavy chain chromosome region. The most recent of these loci to be demonstrated (Ig-5, determining the δ chain)3 was detected by the reaction of alloantisera prepared against spleen cells from mice differing in both H–2 and allotype. These sera reacted with B lymphocytes of the appropriate allotype congenic strains, as assessed by either immunofluorescence, or cell surface iodination and polyacrylamide gel electrophoresis (PAGE). As most B lymphocytes express cell surface IgM as well as IgD (refs 4–6), we have further pursued these various approaches to identify Ig allotypes and have found a polymorphism of the heavy chain (μ) of murine IgM, a molecule found in pentameric form (19S) in serum, and in monomeric (8S) form on the surface of lymphocytes. This defines a locus, Ig-6, which encodes the μ chain of most mouse IgM immunoglobulin.

The problem of the evolution and inheritance of gene loci polymorphic for alleles with extensively differing sequences has been raised by the finding that the rat immunoglobulin κ-chain allotypes, RI-1a and RI-1b, which segregate as co-dominant alleles1–5, differ at 11 out of 107 amino acid positions6. It has been proposed that such ‘complex allotypes’ may represent the products of duplicated genes, analogous to immunoglobulin isotypes, which are subject to allelic regulation (see ref. 7 for a review). The present study was designed to determine the number and identity of the genes for κ-chain allotypes in the genome of inbred laboratory rats; if these allotypes represent duplicated genes it should be possible to identify the RI-1a structural gene in an inbred strain which only expresses the RI-1b allotype, or vice versa. Thus a gene corresponding to the RI-1b constant region of the κ light chain (Cκ) was cloned from LOUVAIN (LOU) rat liver DNA, and then used as a hybridization probe to analyse liver DNA from LEW (RI-1b) and DA (RI-1a) strains of rat8. The results reported here indicate that the genome of each inbred strain contains a Cκ gene of only the appropriate RI-1 type. Therefore the complex RI-1 allotypes in the rat cannot be explained by duplicated genes but by an unusual evolutionary history.