Apparent trans-chromosomal antibody class switch in mice bearing an Igh(a)mu-chain transgene on an Igh(b) genetic background

Native high molecular weight dextran induces a thymus-independent response in BALB/c mice. When the dextran epitope is linked to a protein carrier the response becomes thymus-dependent. IgG antibodies produced after secondary immunization had epitope specificity and idiotope of myeloma M104E. The an tibody of M104E (mu, lambda(1)) is representative for antibodies produced b y mice with immunoglobulin haplotype Igh(a) in response to immunization wit h dextran B1355S. Myeloma product and physiological antibodies share specif icity for the alpha(1-3) glucosidic linkage and have idiotopes in common. M ice with halpotypes other than Igh(a) (e.g. Igh(b)) are unable to yield thi s type of response. A complete rearranged immunoglobulin mu-chain gene with a VDJ-region from BALB/c (Igh(a)) myeloma protein M104E had been introduce d into the genome BALB/c congenic mice having the haplotype Igh(b). As was shown previously in our laboratory the M104E mu-chain transgene confers Igh (a)-type reactivity to Igh(b) mice. In experiments described in this report we used the thymus-dependent form o f the antigen to immunize mice bearing the M104E mu-chain, either alone or together with the lambda(1)-chain, as a transgene on an Igh(b) genetic back ground. Serological analysis revealed a class switch to IgG very similar to that seen in BALB/c mice with respect to magnitude, kinetics, epitope and idiotope specificity. The pattern of IgG subclass expression was indistingu ishable in mu-chain transgenic Igh(b) and normal BALB/c mice. The class swi tch occurred even though, as is shown here, the transgene had become incorp orated in a site not linked to the Igh locus on chromosome 12. We propose a model for this apparent trans-chromosomal class switch recombination which is based on mechanisms known for conventional switch recombination.