Many lines of evidence suggest that autoimmune diseases are the result of chronic immune activation in genetically susceptible individuals following specific environmental exposures. Although the rarity and heterogeneity of autoimmune diseases and the lack of understanding of pathogenetic mechanisms have inhibited progress in the field, genes encoding histocompatibility molecules, immunoglobulins, complement components, peptide transporter proteins, T-cell receptors, sex hormones, cytokines, and metabolic enzymes important in drug and toxin elimination, have been identified as risk factors for one or more autoimmune diseases. Novel molecular genetic techniques and epidemiologic approaches that subset diseases by demographics, clinical manifestations, serology, and environmental exposures, should further elucidate the environmental and genetic risk factors for these increasingly recognized multifactorial disorders.

Signal transducer and activator of transcription 6 (STAT6) is essential for the biological activities of interleukin-4 (IL-4) and the development of allergic responses in mice. Here we report on a sensitive and specific assay for STAT6 activation in response to IL-4. We took advantage of double-stranded oligonucleotide probes containing a STAT6-binding gene-sequence from the promotor of the immunoglobulin heavy chain germline Ε transcript to study the IL-4-induced DNA binding of STAT6. Using these probes, we show that repeated adjacent STAT6-binding sites result in enhanced STAT6-DNA binding. Moreover, the distance between the binding sites is critical for STAT-DNA binding, i.e. STAT6 binding is decreased at distances above 20 nucleotides between neighbouring binding sites. Using this assay to study cross-talk between IL-4 and chemokines, we provide evidence that MIP-1β and MIG inhibit IL-4-induced STAT6 activation, whereas other chemokines and cytokines do not. In conclusion, our data show that oligonucleotide fishing is a supplementary tool for studying cytokine cross-talk at a genomic level.

‘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.

The class II transactivator is a major transcriptional factor acting on the promoters of MHC class II genes. Transcription of the CIITA gene is driven by four alternative promoters, which exhibit cell-type-specific activity. The CIITA promoter III (PIII) is constitutively active in B cells, whereas promoter IV (PIV) becomes activated upon interferon-γ activation. The aim of this study was to investigate whether these two promoters exhibit a sequence variability like the MHC class II promoters do. We isolated PIII and PIV fragments from healthy individuals and rheumatoid arthritis patients and screened them for sequence polymorphisms. Single base pair substitutions within the CIITA PIV were found in 9% of the individuals analyzed. The majority of the substitutions were located upstream of the known cis-acting elements of the promoter. PIII was non-polymorphic. To evaluate the functional relevance of the detected polymorphism we cloned variable PIV upstream of the luciferase reporter gene. Such prepared constructs were transfected into monocytes, melanoma and HeLa cells, which were subsequently stimulated with interferon-γ. The analysis of promoter activities did not reveal significant differences in all three cell types. We conclude that the level of CIITA expression does not vary within the population. Thus the differences in the level of MHC class II expression, which are observed between individuals, stem for the polymorphisms of the MHC class II promoters themselves.

The aim of the present study was to compare the frequencies of the F allele of C3 complement component and the Leiden mutation of coagulation factor V in patients with severe coronary heart disease (CHD) who survived myocardial infarction (MI; group A), and those who had no MI in their case history (group B). We have determined the C3 allele frequencies by electrophoresis, and Leiden mutation by PCR in 338 patients with severe CHD and in 490 and 523 healthy controls, respectively. The C3*F allele frequency was significantly (p = 0.006) higher in group A (0.213) that in group B (0.132). A significant (p = 0.045) difference was found between ≤60-year group A (0.077) and group B (0.029) patients in the frequency of Leiden mutation. These findings indicate that the C3*F allele and the Leiden mutation may be associated with an increased risk of developing myocardial infarction in CHD patients.

‘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.