DIFFERENTIAL EXPRESSION OF 13 IGA-HEAVY CHAIN GENES IN RABBIT LYMPHOID-TISSUES

Molecular cloning techniques have recently demonstrated that rabbit ha s 13 different IgA Calpha H chain genes. This is in contrast to human and mouse that have only two and one Calpha heavy chain genes, respect ively. In previous studies, nucleotide sequence analysis indicated tha t the 13 rabbit Calpha genes were potentially functional, and in vitro expression experiments showed that at least 12 of these genes were ex pressible. To understand the role of these multiple IgA isotypes we an alyzed RNA of various lymphoid tissues for the presence of mRNA repres enting each of the multiple Calpha genes. We used the RNase protection assay with probes that are specific for the 13 different Calpha genes and we consistently found that at least 10 of the Calpha genes are ex pressed, albeit at different levels, in gut (small intestines), append ix, mesenteric lymph node, and mammary tissue. However, in salivary gl and (subman-dibular), only seven of these genes are expressed at signi ficant levels and in lung and tonsil only one Calpha gene, Calpha 4, i s expressed at a level comparable to its expression in other tissues. Analysis of RNA of Peyers patch showed differences in the level of Cal pha gene expression between different animals and between different Pe yers patches of the same rabbit; in some cases, most of the Calpha gen es were expressed, but in some cases only Calpha 4 was expressed at a significant level. Inasmuch as Calpha 4 is the 5' most Calpha gene we propose that IgA-producing cells are derived from B cells that have in itially undergone isotype switching to Calpha 4 and we discuss various mechanisms that could explain switching to the more 3' Calpha genes.