In vivo expression of human immunoglobulin germ-line mRNA in normal and in immunodeficient individuals

Abstract

Previous in vitro studies suggest that transcription of the unrearranged immunoglobulin switch region and its 5′ flanking region precedes isotype switching. These transcripts, which arc devoid of a variable region, contain unique exons and are called germ‐line (GL) mRNA. A crucial point in this regard is whether such transcripts could be detected in vivo, and if their expression correlates with immunoglobulin class switching in health and disease. To understand the in vivo role of this transcriptional activity we have adapted the reverse transcription‐polymerase chain reaction (PCR) to analyse the GL transcripts from unstimulated peripheral blood mononuclear cells (PBMC) in healthy individuals and in different immunological diseases. Furthermore, mononuclear cells from different human organs were also analysed. We report here that GL (Iα. Iγ and Iɛ used lo designate the GL mRNA for IgA. IgG and IgE, respectively) nRNA are expressed differentially during ontogeny of B cells. Unexpectedly, no difference of Iα mRNA expression between the PBMC and the secondary lymphoid organs was detected. Rather. the levels of GL transcripts were correlated to ihe number of sIgM⁺ cells. GL mKNA of all three isotypes could be detected in PBMC from healthy donors, whereas there was a decrease of specific GL transcript synthesis in individuals with Immunoglobulin deficiency. Furthermore, during the in vivo immune response in a parasitic infection, we could demonstrate an induction of GL k mRNA during in vivo immune response. Concomitantly. there was also increased synthesis of productive F. transcripts. These findings implicate a potential role of GL transcription during in vivo immunoglobulin class switching.