Search PubMed⌕ Search

Biomedical subjects

G Lefranc

Publications and source records attributed to G Lefranc.

At least 55 records · Page 3Linked to original sources

Polymorphism of the T-cell receptor gamma variable and constant region genes in a Chinese population.

The human T-cell receptor gamma gene region spans 160 kb genomic DNA. Restriction fragment length polymorphisms (RFLPs) have been previously documented for the constant region (TRGC) genes, the joining (TRGJ) segments and the variable (TRGV) genes. We have recently defined the alleles of the T-cell receptor gamma V, J and C genes and we have described seven haplotypes of the V gamma subgroup I genes characterized either by RFLPs or by deletion or insertion of V gamma genes. The number of V gamma I genes may vary from 7 to 10 per haploid genome, the 9-gene haplotype being the most frequent. Allelic fragments can unambiguously characterize the TRGC2 gene with duplication or triplication of the exon 2. These alleles and haplotypes have been analyzed in four different populations (French, Lebanese, Tunisian and Black African). In this paper, we compare these allele and haplotype frequencies with those found in a Chinese population and we describe new TRGV allelic restriction fragments found only in the Chinese samples. These results and the previous data demonstrate the flexibility of the human T cell receptor gamma locus and the importance of unequal crossing-overs in the evolution of that locus. Moreover, they underline the importance of studying these polymorphisms in population genetics.

Alleles↗

Process for analysis of an area delimited by a nonparametric curve and divided into microdomains, and for localization of possible constituents: exploitation by "digisector" software.

The process presented here was designed and developed for study of various cell parameters in electron microscopy photographs and analysis of the location of certain differentiated cell-constituents relative to plasma membrane. It can also be used for many other applications, for example, in metallurgy, petrography and geostrategy. A photograph is analyzed using a plotting table interfaced with a microcomputer.

Image Processing, Computer-Assisted↗

Three-dimensional analysis demonstrates the presence of exocrine cytoplasmic vela between endocrine cells and basal lamina in the stomach of mammals.

Three-dimensional analysis demonstrated the presence of cytoplasmic vela extending from exocrine cells into the space between endocrine cells and basal lamina in the gastrointestinal epithelium of the rabbit; these structures were also observed in various other mammals. The following techniques were used to determine the morphologic characteristics of these vela and to study their significance: preparation of semiserial thin sections, three-dimensional reconstruction in plexiglass and lanthanum staining of pericellular spaces. It was found that these fine vela, devoid of major differentiated cell-constituents, sometimes form a pseudocircular crown at the base of endocrine cells. If the zone of basal apposition of the plasma membrane is referred to as ZBA and the zones of lateral apposition as ZLA, the presence of this velum makes it possible to distinguish a zone of immediate apposition without interposition (ZIA) and a mediate zone of apposition with interposition (ZMA) within the ZBA. Exocrine cell processes can also penetrate within endocrine cells in invaginations, and the depth of these invaginations can be demonstrated by lanthanum staining. Adjacent to the membrane zones defined above, other cytoplasmic microdomains-M(ZLA) and M(ZBA), as well as M(ZIA) and M(ZMA) of different morphofunctional significance may also be envisaged.

Animals↗

Reciprocal hybrid joints demonstrate successive V-J rearrangements on the same chromosome in the human TCR gamma locus.

Novel variable (V)--joining (J) gene rearrangements are described in the human T cell receptor gamma locus, in which, on the one hand, the V3 variable gene is joined to the heptamer--nonamer recombination signals of the J1 segment and, on the other hand, the J1 segment is joined to the V3 recombination signals through head-to-head fusion. These recombination products, or hybrid joints, have been originated through an inversion of 47 kb DNA. Interestingly the inverted DNA stretch contains a normal V9-J9 rearrangement. These findings are the first direct demonstration that successive rearrangements occur, on the same chromosome, in the human T cell receptor gamma locus, and suggest that the chronology of the joining events plays a role in the ontogeny of T cells and their differentiation in gamma/delta + and alpha/beta + lineages.

Amino Acid Sequence↗

[Immunogenetic markers (BF, C2, C4, 21-OH, TNF alpha, TCR beta, Ig) and insulin-dependent diabetes in the Tunisian population: serological and molecular study].

48 Tunisian people suffering from the IDDM auto-immune disease were compared to 35 control healthy persons for the polymorphisms of the complement BF, C2 and C4 proteins and genes, of the IgG (Gm allotypes) as well as of the TNF alpha and TCR C beta genes. Our study shows that the BFF1-C4A3-C4BQO and BFS-C4AQ0-C4B1 complotypes are associated to IDDM (RR of 2.97 and 3.07 respectively), as previously reported for other circummediterranean populations. The frequency of the Gm 21.28; 1.17; .. haplotype is increased, but not significantly, among the patients. The RFLP analysis reveals that the 2.65 kb SacI allelic restriction fragment of the C2 gene may be considered as a genetic marker of susceptibility to IDDM because its frequency raises to 0.206 among the patients vs 0.021 in the healthy individuals (p less than 0.001). The frequencies of the C4AQ0 and C4BQ0 alleles are more important among the IDDM patients than within the control sample, but the only C4BQ0 allele frequency is significantly increased. Both C4AQ0 and C4BQO result mainly from deletions. The frequencies of the allelic restriction fragments of the TNF alpha and TCRC beta genes are not significantly different among the patients and the controls. But the small sample size don't allow us to conclude definitively. It would be very interesting to extend the RFLP analysis to the TCR V beta and V alpha gene regions on more numerous samples.

Adolescent↗

Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis.

Single and extensive multigene deletions have been described in the Ig CH immunoglobulin heavy-chain constant region genes, some of these encompassing up to 160 kilobases. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their findings; deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP-G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly in the Mediterranean area. The high level of consanguinity in the Tunisian population accounts for the high frequency of individuals homozygous for one or the other of these multigene deletions which involve highly homologous regions as hot spots of recombinations, outside of the switch sequences, in the Ig CH locus. In 15 cases out of 16, these multigene deletions have been observed in healthy people, although these individuals lacked several immunoglobulin subclasses and, even, one class. Such an immunological situation makes it possible to study the importance of these subclasses for the overall immunity, and to analyse the specific immune responses by the retained IgG and IgA subclasses.

Chromosome Deletion↗

Rearrangements of immunoglobulin light and heavy chain genes and correlation with phenotypic markers in B-cell chronic lymphocytic leukemia.

Twenty-five patients with B-cell chronic lymphocytic leukemia (B-CLL) were investigated to correlate the immunological phenotype with the description of the Ig gene rearrangements of the B-cell clone. All patients were positive for the CD19 antigen and one pan B-antigen, markers of late cells (CD20, CD37 or Y2955). Twenty-four of the 25 patients tested expressed monoclonal cell surface immunoglobulin (SIg). The CD5 antigen was present in 21 of the 25 tested patients. Immunoglobulin gene rearrangements were detected by hybridization of the BamHI, EcoRI, BgIII, and HindIII digested genomic DNAs to the IGHJ, IGKC, IGLC, and IGLJ2 probes. Twenty-four of 25 patients had two rearranged IGH loci. The IGKC rearrangements were observed in 20 patients. In four patients, the IGK loci were deleted on both chromosomes. One patient without SIg displayed a germline pattern. All six patients with lambda producing B-CLL showed a lambda gene rearranged band, although the use of IGL polymorphism to investigate IGL rearrangements must be noted. These clonal rearrangements of IGL genes, together with the detection of either the kappa or lambda light chain of SIg, confirm that patients with B-CLL meet the developmental scheme of ordered light chain gene rearrangements.

B-Lymphocytes↗

Subclass distribution of antigen-specific IgA antibodies in normal donors and individuals with homozygous C alpha 1 or C alpha 2 gene deletions.

To analyze the subclass restriction of Ag-specific IgA, sera and saliva from healthy blood donors and from IgA class or subclass deficient individuals were studied. The latter included donors with or without C alpha 1 or C alpha 2 gene deletions. Monoclonal human IgA1 and a genetically engineered IgA2 antibody, normal human serum and colostrum IgA were used as standards to estimate serum and saliva levels of Ag-specific antibodies. In normal individuals, there was a strong IgA1 preference of naturally acquired antibodies in serum against both polysaccharide Ag (PPS 6A, PPS 23, pneumococcal C-polysaccharide, and LPS from Escherichia coli) and protein Ag (Staphylococcus aureus alpha-toxin and HSV). Specific IgA2 in serum against the tested Ag were frequently not measurable. In contrast, most of the individuals with homozygous C alpha 1 gene deletions displayed substantial amounts of specific IgA2 against protein as well as polysaccharide Ag. The median levels of specific IgA in serum against protein Ag were approximately one-third as compared to normal individuals and one-fifth, or less, against polysaccharide Ag. Normal serum levels of IgA against the tested Ag, restricted to the IgA1 subclass, were noted in two individuals with IgA2 deficiency, one of whom carried a homozygous C alpha 2 gene deletion. Median values of specific IgA, against the tested Ag S. aureus alpha-toxin, HSV, and pneumococcal C-poly-saccharide, from normal healthy donors were approximately four to eight times higher in serum as compared to saliva. Individuals with homozygous C alpha 1 gene deletions displayed increased levels of the various specific IgA2 antibodies in saliva. In conclusion, the individuals with homozygous C alpha 1 gene deletions displayed decreased median levels of specific IgA antibodies in serum despite normal levels of total IgA. Normal levels of both specific IgA and total IgA in saliva were found.

Chromosome Deletion↗