Early occurrence of immunoglobulin isotype switching in human fetal liver

Abstract

A cDNA library prepared from a human fetal liver of the first trimester of gestation was screened with Ig Cμ, Cγ, Cκ and Cλ probes. Ten heavy chain clones were isolated and characterized by restriction mapping and partial sequencing. The absence of Ig light chain clone and the presence of pre-B-specific λ-like transcripts suggest that the immune compartment of this cDNA library was mostly derived from pre-B cells. Three transcripts of μ, γ2 and γ4 isotypes contained a V-D-J-C region with an open reading frame and used members of the V HIV, V HIII and V HI families, respectively. Seven clones were derived from sterile transcripts, one Cμ and six Cγ. In addition to Cμ exons, the sterile μ transcript contained the 5' flanking germline region. By contrast, the γ sterile transcripts used a 5' sequence that was spliced from the Iγ 1 region onto the first Cy 1 exon. In addition several of these transcripts were derived from alternative splicing. The simultaneous expression of both sterile and functional y transcripts suggests that the switch mechanism operates in normal fetal liver very early in ontogeny.