DISTRIBUTION OF HLA‐G ALTERNATIVE mRNAs INCLUDING SOLUBLE FORMS IN NORMAL LYMPHOCYTES AND IN LYMPHOID CELL‐DERIVED LEUKEMIA

The non‐classical HLA‐G gene is the only class I antigen expressed in trophoblasts at the maternofetal interface. In placenta, the HLA‐G gene produces several alternatively spliced isoforms encoding bound‐membrane proteins (G1, G2, G3 and G4) lacking, respectively, exon 7; exons 7 and 3; exons 7, 3 and 4, and exons 7 and 4. In addition, two isoforms (G1s and G2s) containing an intron 4 sequence are able to encode soluble antigens. We have recently reported that the HLA‐G gene is transcriptionally active in lymphocytes and is not transcribed in CD34+ cells, polynuclear cells or monocytes. To investigate the functional significance of the different isoforms in lymphocytes, we studied their distribution in normal T and B lymphocytes and in malignant lymphoid cells by using the RT‐PCR technique followed by hybridization with exon‐specific probes and sequencing assays. In transcriptionally active lymphocytes, the HLA‐G primary transcript is the major form and is differentially spliced in B and T lymphocytes: (i) G1s is found in several samples of T and B cells whereas G2s is only transcribed in T lymphocytes, (ii) the G4 isoform is never detected in B lymphocytes. In addition, we have shown that HLA‐G is inactive in some samples of lymphocytes. Our data suggest that HLA‐G transcription is regulated at the initiation level and at the subsequent splicing. These two levels of regulation may be dysregulated in some cases of T‐ALL and CLL. The potential functions of the HLA‐G alternative forms in lymphocytes, such as peptide binding and modulation of the immune response, are discussed.