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PubMed1989

The HLA-DRw8 lineage was generated by a deletion in the DR B region followed by first domain diversification.

Sequences were generated for the first, second, and 3'UT regions of DRw8 beta-chain genes from two cell lines differing in their T cell determined allospecificities. Both have second domain sequences homologous to the B1 locus of the DRw52 family (DR3, DR5, and DRw6) and not the B3 locus. However, the 3'UT sequence is homologous to the 3'UT region of the B3 locus of the DRw52 family, and not the B1 locus. The first domain sequences are B1-like as opposed to B3-like and show polymorphism in the region encoding the putative alpha-helical region of the DR beta-chain. The easiest interpretation is that the DRw8 haplotypes constitute a sublineage within the DRw52 group and that this lineage has arisen by a small chromosomal deletion of the region between the B1 locus and the B3 locus. This deletion included the 3'UT region of the B1 locus, the B2 pseudogene, and the 5' end of the B3 locus including the exons encoding the first and second domains. After the deletion, two changes in the first domain arose by a mutational mechanism, possibly gene conversion. One of these changes parallels one seen in the DRw11 lineage.

Amino Acid Sequence↗
PubMedDate not supplied

Autoantibody production in Sjögren's syndrome: a hypothesis regarding defects in somatic diversification of germ line encoded genes.

Patients with primary Sjögren's syndrome (SS) have rheumatoid factor (anti-IgG Fc antibody, RF) in their sera that contains a crossreactive idiotype (CRI) defined by monoclonal antibody 17-109. This CRI is shared by SS patients and certain patients with Waldenstrom's macroglobulinemia. This CRI was not found in increased frequency in RF from rheumatoid arthritis patients lacking SS. The structural basis for this CRI is the highly conserved kappa chain of the Vk IIIb sub-subgroup. In SS patients, the CRI is present on both IgA RF and IgM RF, accounting for 5-20% of the total RF. Recent studies have shown that a germ line encoded kappa variable region gene (Humkv 325, cloned from a placental DNA library) has DNA sequence that encodes the variable region amino acid sequences of CRI positive kappa chains. Using MoAb 17-109, we have been able to determine the tissue distribution of CRI+ B-cells. We found an increased frequency in the salivary gland biopsies of SS patients and also in their intestinal mucosal tissues (i.e. Peyer's patch). In comparison, we also detected an increased frequency of CRI+ B-cells in the Peyer's patch regions of normals. Taken together, these results suggest that CRI+ B-cells may play an important role in normal mucosal immunity and these CRI+ B-cells have migrated to the salivary gland in SS patients as part of the inflammatory process directed at autoantigens or exogenous antigen(s) located at a mucosal surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1986

The application of aqueous two-phase partition to the study of chick limb mesenchymal diversification.

A technique which identifies cells differing in surface character, aqueous two-phase partition using thin-layer countercurrent distribution (TLCCD), has been used to study differentiation and pattern formation in the developing chick limb bud. The TLCCD profiles of cell populations, derived from various regions of morphologically undifferentiated mesenchyme from three different stages of limb development, have been compared. At no stage, or location, has the population been found to be homogeneous. Cells from progress zones and more proximal regions could all be resolved into several populations. The populations from progress zones at three different developmental stages were qualitatively similar but differed in the proportions of cells in each. The most striking differences in cell populations were those obtained from the most proximal region of the limb, closest to the flank, which represents the developmentally most advanced region.

Animals↗