Analysis of somatic hypermutations of immunoglobulin gene rearrangements in childhood acute lymphoblastic leukemia.

The current study investigated the presence, frequency, and status of somatic hypermutations as well as their role in children with B lineage ALL. The obtained sequences were analyzed using IMGT/V-QUEST. Totally, 150 IGH sequences were evaluated; 139 from the 111 patients at the time of diagnosis and 11 from 8/111 patients at the time of relapse. The findings of the current report revealed the presence of somatically mutated V genes in childhood B lineage ALL. A higher frequency of somatic hypermutations was noted in unproductive rearrangements and was generally attributed to nucleotide mutation type, region, and IGHV gene subgroup biases.

T cell diversity and TcR repertoires in teleost fish.

In vertebrates, the diverse and extended range of antigenic motifs is matched to large populations of lymphocytes. The concept of immune repertoire was proposed to describe this diversity of lymphocyte receptors--IG and TR--required for the recognition specificity. Immune repertoires have become useful tools to describe lymphocyte and receptor populations during the immune system development and in pathological situations. In teleosts, the presence of conventional T cells was first proposed to explain graft rejection and optimized specific antibody production. The discovery of TR genes definitely established the reality of conventional T cells in fish. The development of genomic and EST databases recently led to the description of several key T cell markers including CD4, CD8, CD3, CD28, CTLA4, as well as important cytokines, suggesting the existence of different T helper (Th) subtypes, similar to the mammalian Th1, Th2 and Th17. Over the last decade, repertoire studies have demonstrated that both public and private responses occur in fish as they do in mammals, and in vitro specific cytotoxicity assays have been established. While such typical features of T cells are similar in both fish and mammals, the structure of particular repertoires such as the one of gut intra-epithelial lymphocytes seems to be very different. Future studies will further reveal the particular characteristics of teleost T cell repertoires and adaptive responses.

The deduced structure of the T cell receptor gamma locus in Canis lupus familiaris.

Analyzing the recent high-quality genome sequence of the domestic dog (Canis lupus familiaris), we deduced for the first time in a mammalian species belonging to Carnivora order, the genomic structure and the putative origin of the TRG locus. New variable (TRGV), joining (TRGJ) and constant (TRGC) genes for a total of 40 are organized into eight cassettes aligned in tandem in the same transcriptional orientation, each containing the basic recombinational unit V-J-J-C, except for a J-J-C cassette, that lacks the V gene and occupies the 3' end of the locus. Amphiphysin (AMPH) and related to steroidogenic acute regulatory protein D3-N-terminal like (STARD3NL) genes flank, respectively, the 5' and 3' ends of the canine TRG locus that spans about 460kb. Moreover LINE1 elements, evenly distributed along the entire sequence, significantly (20.59%) contribute to the architecture of the dog TRG locus. Eight of the 16 TRGV genes are functional and belong to 4 different subgroups. Canine TRGJ genes are two for each cassette and only seven out of 16 are functional. The germline configuration and the exon-intron organization of the 8 TRGC genes was determined, six of them resulting functional. The dot plot similarity genomic comparison of human, mouse and dog TRG loci highlighted the occurrence of reiterated duplications of the cassettes during the dog TRG locus evolution. On the other hand the low ratio of functional genes to the total number of canine TRG genes (21/40), suggest that there is no correlation between the extensive duplications of the cassettes and a need for new functional genes. Furthermore the comparison revealed that the TRGC6, C7 and C8 genes are highly related across species suggesting these existed before the primate-rodent-canidae lineages diverged.

Characterization of human FCGR3B*02 (HNA-1b, NA2) cDNAs and IMGT standardized description of FCGR3B alleles.

The low-affinity Fc gamma receptor IIIb (Fc gamma RIIIb and CD16b) is constituted by a unique FCGR3B polypeptide chain that comprises two extracellular immunoglobulin-like domains, and is expressed as a glycosylphosphatidyl inositol-anchored receptor on the neutrophils. The FCGR3B chain bears allotypes that define the human neutrophil antigen-1 (HNA-1 and NA) system involved in major post-transfusional reactions. FCGR3B is highly homologous to FCGR3A, which is expressed as a transmembrane receptor on natural killer cells and monocytes/macrophages. Its transcription products were not yet fully characterized. In the present work, we sequenced FCGR3B cDNAs with complete 3' untranslated region from purified granulocytes of HNA-1b/HNA-1b (NA2/NA2) genotyped donors. We characterized two FCGR3B cDNAs of different lengths corresponding to two polyadenylation sites. This result was corroborated by data raised by serial analysis of gene expression (SAGE). FCGR3B allele polymorphisms, from this article [FCGR3B*02 (HNA-1b, NA2)] and from the literature, are described for the first time according to the IMGT standardized nomenclature and to the IMGT unique numbering for C-LIKE-DOMAIN (http://imgt.cines.fr). These rules, described in the IMGT Scientific chart, are based on the IMGT-ONTOLOGY concepts. IMGT allele alignments and IMGT Collier de Perles graphical two-dimensional representations are provided for the two Ig-like domains (or C-LIKE-DOMAINs) [D1] and [D2] of FCGR3B*02. The standardized description of FCGR3B allele polymorphisms was approved by the IMGT Nomenclature Committee (IMGT-NC) and is freely available in IMGT repertoire at IMGT, http://imgt.cines.fr.

IMGT databases, web resources and tools for immunoglobulin and T cell receptor sequence analysis, http://imgt.cines.fr.

IMGT, the international ImMunoGeneTics database((R)) (http://imgt.cines.fr), is a high-quality integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates, created in 1989, by LIGM, at the Université Montpellier II, CNRS, Montpellier, France. IMGT provides a common access to standardized data which include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT includes several databases (IMGT/LIGM-DB, IMGT/3Dstructure-DB, IMGT/HLA-DB), Web resources ('IMGT Marie-Paule page') and interactive tools (IMGT/V-QUEST, IMGT/JunctionAnalysis). IMGT expertly annotated data and tools described in this paper are particularly useful for the analysis of the IG and TR rearrangements in leukemia, lymphoma and myeloma, and in translocations involving the antigen receptor loci. IMGT is freely available at http://imgt.cines.fr.

Nomenclature of the human immunoglobulin kappa (IGK) genes.

'Nomenclature of the Human Immunoglobulin Kappa (IGK) Genes', the 17th report of the 'IMGT Locus in Focus' section, provides the first complete list of all the human IGK genes. In the most frequent haplotypes, the human IGK locus spans 1,820 kb and the IGKV genes are organized in two clusters separated by 800 kb. In those haplotypes where both the proximal and distal IGKV clusters are present, the total number of human IGK genes per haploid genome is 82 (107 genes if the orphons are included) of which 37-41 are functional. If only the proximal IGKV cluster is present, which is found in a rare haplotype, the total number of genes per haploid genome is 46 (71 genes if the orphons are included) of which 23-25 genes are functional. IMGT/HUGO gene names and definitions of the human IGK genes on chromosome 2p11.2, and IGK orphons on chromosomes 1, 2, 15, and 22 are provided with the gene functionality and the number of alleles according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences, and the accession ID of the Genome Database GDB and NCBI LocusLink databases in which all the IMGT human IGK genes have been entered. The tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

IGHV3-associated restriction fragment length polymorphisms confer susceptibility to bullous pemphigoid.

OBJECTIVE: To determine whether the immunoglobulin heavy chain genes contribute to the occurrence of bullous pemphigoid (BP), polymorphisms of both the immunoglobulin constant IGHC and variable IGHV groups were studied in 100 Caucasian BP patients and 143 ethnically matched healthy individuals. METHODS: To analyze the restriction fragment length polymorphism (RFLP) of the IGHG constant locus, a genomic immunoglobulin gamma 3 probe which detects polymorphisms in the gamma constant genes was hybridized to BstEII- or BamHI/SacI-digested germline DNA, while IGHV3 subgroup polymorphism was analyzed by hybridizing a cloned VH3 probe to EcoRI-digested DNA. RESULTS: No difference in the frequencies of the genotypes defined by the constant probe was observed between patients and controls. Analysis of the RFLP obtained with the VH3 probe showed that within the range of 4.5 and 1.5 kb, the observed band pattern was composed of 8 monomorphic and 7 polymorphic bands. Among the latter, 4 allowed to define 10 different restriction patterns. One pattern was shown to be significantly less frequent in patients than in controls. CONCLUSION: IGHV3 polymorphism might be a factor conferring susceptibility to BP.

Nomenclature of the human immunoglobulin heavy (IGH) genes.

'Nomenclature of the Human Immunoglobulin Heavy (IGH) Genes', the 16th report of the 'IMGT Locus in Focus' section, provides the first complete list of all the human IGH genes. The total number of human IGH genes per haploid genome is 170-176 (206-212 genes, if the orphons and the processed gene are included), of which 77-84 genes are functional. IMGT/Human Genome Organization (HUGO) gene names and definitions of the human IGH genes on chromosome 14q32.33, processed gene on chromosome 9 and IGH orphons on chromosomes 15 and 16 are provided with the gene functionality and the number of alleles, according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences and with the accession ID of the Genome Database GDB and NCBI LocusLink databases, in which all the IMGT human IGH genes have been entered. The tables are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

The mouse (Mus musculus) T cell receptor delta variable (TRDV), diversity (TRDD) and joining (TRDJ) genes.

'The Mouse (Mus musculus) T Cell Receptor Delta Variable (TRDV), Diversity (TRDD) and Joining (TRDJ) Genes', the 15th report of the 'IMGT Locus in Focus' section, comprises 7 tables entitled: (1) 'Number of mouse (Mus musculus) germline TRDV genes at 14D1-D2 and potential repertoire'; (2) 'Mouse (Mus musculus) germline TRDV genes at 14D1-D2'; (3) 'Mouse (Mus musculus) TRDV allele table'; (4) 'Mouse (Mus musculus) germline TRDD genes and alleles'; (5) 'Mouse (Mus musculus) germline TRDJ genes'; (6) 'Mouse (Mus musculus) TRDJ allele table', and (7) 'Correspondence between the different mouse (Mus musculus) TRDV gene nomenclatures'. These tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines. fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France.

Nomenclature of the human immunoglobulin lambda (IGL) genes.

'Nomenclature of the Human Immunoglobulin Lambda (IGL) Genes', the 18th report of the 'IMGT Locus in Focus' section, provides the first complete list of all the human IGL genes. The total number of human IGL genes per haploid genome is 87--96 (93--102 if the orphons are included), of which 37--43 genes are functional. IMGT/Human Genome Organization (HUGO) gene names and definitions of the human IGL genes on chromosome 22q11.2 and IGL orphons on chromosomes 8 and 22 are provided with the gene functionality and the number of alleles, according to the rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences and with the accession ID of the Genome Database GDB and NCBI LocusLink databases, in which all the IMGT human IGL genes have been entered. The tables are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

Nomenclature and overview of the mouse (Mus musculus and Mus sp.) immunoglobulin kappa (IGK) genes.

'Nomenclature and overview of the mouse (Mus musculus and Mus sp.) immunoglobulin kappa (IGK) Genes', the 19th report of the 'IMGT Locus in Focus' section, provides the first complete list of all the mouse (M. musculus) IGK genes. The mouse (M. musculus) locus spans 3,200 kb. The total number of mouse (M. musculus) IGK genes per haploid genome is 164 (174 if the orphons are included). The functional genomic repertoire comprises 93 IGKV belonging to 18 subgroups, 5 IGKJ and 1 IGKC gene. IMGT gene names and definitions of the mouse (M. musculus) IGK genes on chromosome 6 and IGK orphons are provided with the gene functionality and the number of alleles, according to the concepts of IMGT-ONTOLOGY and to rules of the IMGT Scientific chart, with the accession numbers of the IMGT reference sequences. These tables and figures are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

DNA sequence variability of IGHG3 alleles associated to the main G3m haplotypes in human populations.

The present study investigates the molecular basis of the G3m polymorphism expressed by the heavy constant domains of human immunoglobulins gamma 3 chains. By using a new protocol allowing the specific cloning of IGHG3 genes, a total of 51 full-length IGHG3 genomic sequences (about 2 kb) isolated from African, Siberian, West Asian and European population samples were sequenced. IGHG3 sequences were assigned precise G3m haplotypes on the basis of specific associations between G3m allotypes and IGHG3 RFLPs. Specific DNA substitutions involved in the expression of G3m(5), G3m(6), G3m(15), G3m(16), G3m(21), G3m(24) and G3m(28) allotypes were then deduced, elucidating almost completely the determination of the G3m polymorphism at the DNA level. The molecular evolution of G3m haplotypes was investigated by a maximum likelihood phylogeny of IGHG3 sequences. Sequence clusters are shown to be G3m haplotype-specific, corroborating the Gm molecular model deduced from serology, and showing that populations differentiation is much more recent than G3m haplotypes differentiation. The widely distributed G3m(5,10,11,13,14) haplotype is likely to be ancestral to the other G3m haplotypes presently found at high frequencies in different continental areas.

IMGT, the international ImMunoGeneTics database.

IMGT, the international ImMunoGeneTics database, freely available at http://imgt.cines.fr:8104, was created in 1989 at the Université Montpellier II, CNRS, Montpellier, France, and is a high quality integrated information system specialising in immunoglobulins, T cell receptors and major histocompatibility complex molecules of human and other vertebrates. IMGT provides researchers and clinicians with a common access to all nucleotide, protein, genetic and structural immunogenetics data. This information is of high value for medical and veterinary research, biotechnology related to antibody and T cell receptor engineering, genome diversity and evolution studies of the immune response.

Protein displays of the human T cell receptor alpha, beta, gamma and delta variable and joining regions.

'Protein Displays of the Human T Cell Receptor Alpha, Beta, Gamma and Delta Variable and Joining Regions', the 13th report of the 'IMGT Locus in Focus' section, comprises 8 figures: (1) 'Protein display of the human TRA V-REGIONs'; (2) 'Protein display of the human TRB V-REGIONs'; (3) 'Protein display of the human TRG V-REGIONs'; (4) 'Protein display of the human TRD V-REGIONs'; (5) 'Protein display of the human TRA J-REGIONs'; (6) 'Protein display of the human TRB J- REGIONs'; (7) 'Protein display of the human TRG J-REGIONs'; (8) 'Protein display of the human TRD J-REGIONs', and 4 tables entitled: (1) 'FR-IMGT and CDR-IMGT length of the human TRAV genes'; (2) 'FR-IMGT and CDR-IMGT length of the human TRBV genes'; (3) 'FR-IMGT and CDR-IMGT length of the human TRGV genes'; (4) 'FR-IMGT and CDR-IMGT length of the human TRDV genes'. These figures and tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http:// imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France.

The mouse (Mus musculus) T cell receptor beta variable (TRBV), diversity (TRBD) and joining (TRBJ) genes.

'The Mouse (Mus musculus) T cell Receptor Beta Variable (TRBV), Diversity (TRBD), and Joining (TRBJ) Genes', the 14th report of the 'IMGT Locus in Focus' section, comprises 8 tables entitled: (1) 'Number of mouse (Mus musculus) germline TRBV genes at 6A-C and potential repertoire'; (2) 'Mouse (Mus musculus) germline TRBV genes at 6A-C'; (3) 'Mouse (Mus musculus) TRBV allele table'; (4) 'Mouse (Mus musculus) germline TRBD genes and alleles'; (5) 'Mouse (Mus musculus) germline TRBJ genes'; (6) 'Mouse (Mus musculus) TRBJ allele table'; (7) 'Correspondence between the different mouse (Mus musculus) TRBV gene nomenclatures'; (8) 'Mouse (Mus musculus) TRBV genes and related human TRBV genes'. These tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France.

The telostei immunoglobulin light IGL1 and IGL2 V, J and C genes.

'Teleostei Immunoglobulin Light IGL1 and IGL2 V, J and C Genes', the 12th report of the 'IMGT Locus in Focus' section, comprises 8 tables: (1) 'Teleostei IGL1V genes'; (2) 'Teleostei germline IGL1J genes'; (3) 'Teleostei IGL1C genes and alleles'; (4) 'Teleostei IGL2V genes'; (5) 'Teleostei germline IGL2J genes'; (6) 'Teleostei IGL2C genes and alleles'; (7) 'FR-IMGT and CDR-IMGT length of the Teleostei IGL1V genes', and (8) 'FR-IMGT and CDR-IMGT length of the Teleostei IGL2V genes'. These tables are available on the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr: 8104) created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

The Teleostei immunoglobulin heavy IGH genes.

'Teleostei Immunoglobulin Heavy IGH Genes', the eleventh report of the 'IMGT Locus in Focus' section, comprises four tables: (1) 'Teleostei IGHV genes'; (2) 'Teleostei germline IGHJ genes'; (3) 'Teleostei IGHC genes and alleles'; (4) 'FR-IMGT and CDR-IMGT length of the Teleostei IGHV genes'. These tables are available at the IMGT Marie-Paule page from IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr: 8104) created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.

The human T cell receptor alpha variable (TRAV) genes.

'Human T Cell Receptor Alpha Variable (TRAV) Genes', the eighth report of the 'IMGT Locus in Focus' section, comprises four tables: (1) 'Number of human germline TRAV genes at 14q11 and potential repertoire'; (2) 'Human germline TRAV genes at 14q11'; (3) 'Human TRAV allele table', and (4) 'Correspondence between the different human TRAV gene nomenclatures'. These tables are available at the IMGT Marie-Paule page of IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104) created by Marie-Paule Lefranc, Université Montpellier II, CNRS, France.