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.
Amiot
L
L
University Laboratory for Hematology and Biology of Blood Cells, University of Rennes I, France.
Onno
M
M
Drénou
B
B
le Marchand
B
B
Lamy
T
T
Semana
G
G
Fauchet
R
R
D017398:Alternative Splicing; D001402:B-Lymphocytes / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000276:immunology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger; D013601:T-Lymphocytes / Q000276:immunology*
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger