PubMed Health⌕ Search

Biomedical subjects

M Weigert

Publications and source records attributed to M Weigert.

At least 55 records · Page 3Linked to original sources
PubMed1985

Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin.

This study focuses on 10 BALB/c anti-influenza virus (A/PR/8/34) hemagglutinin antibodies that have light chains encoded by the same variable region kappa chain (V kappa) gene, V kappa 21C. A comparison of antibodies from lymphocytes of independent origin reveals the contribution of germline diversity (combinatorial joining and association) to this response. Although combinatorial joining and association contribute to sequence diversity, they appear to have little effect on the fine specificity of these antibodies. Somatic mutation, in addition to contributing to the sequence diversity of these antibodies, creates differences in their fine specificity. The extent of mutation and its effect on fine specificity can be seen by comparing antibodies of lymphocytes from the same clone. These intraclonal comparisons also indicate that somatic mutation is an ongoing process occurring at a high rate (estimated to be at least 10(-3) mutations per base pair per division) in the expressed V region heavy chain (VH) and V kappa genes. Furthermore, both the nature and distribution of these mutations suggest that amino acid replacement mutations in the light but not the heavy chain are selected for by antigen.

Animals↗
PubMed1985

Genetic polymorphism at the kappa chain locus in mice: comparisons of restriction enzyme hybridization fragments of variable and constant region genes.

Variable (V kappa) and constant (C kappa) region genes of the mouse kappa light chain have been compared in inbred strains and in geographically isolated or genetically separated populations of mice by Southern blot analysis of endonuclease-restricted germline DNA. In most cases, the C kappa gene is found on a single restriction fragment while the V kappa genes of the V kappa 19 and V kappa 21 groups are each found on several (6-18) fragments. The restriction fragment (RF) patterns of V kappa 19 and V kappa 21 groups are both polymorphic when compared among inbred mouse strains. Southern blot patterns of V kappa 21 and V kappa 19 of inbred strains are also found among some geographically isolated populations of mice, suggesting that inbred strains acquired kappa loci from different subspecies. Some populations of geographical isolates show V kappa 21, V kappa 19, and C kappa contexts similar to inbred mice while more distantly related species within the genus Mus and laboratory rats show no apparent similarity in context to inbred strains. Variable region genes determining the RF patterns of V kappa 19 and V kappa 21 appear to be linked to each other and to the C kappa and Lyt-3 loci.

Animals↗
PubMed1984

Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin.

We have examined the amino-terminal sequence of the kappa light chains of a set of monoclonal antibodies specific for one of the major antigenic determinants (Sb) on the influenza virus PR8[A/PR/8/34(H1N1)] hemagglutinin molecule. This set was believed to be structurally related from earlier serological analysis that typed these kappa chains as members of the variable (V) region V kappa 21 group [ Staudt , L. M. & Gerhard , W. (1983) J. Exp. Med. 157, 678-704]. Our sequence analysis confirms and extends this conclusion; all examples of this set belong to a subgroup of the V kappa 21 group, V kappa 21C . A special feature of this set of kappa light chains is that all examples were derived from the same mouse (designated H36 ). This sequence analysis along with the characterization of gene rearrangements at the kappa light chain loci of these hybridomas is consistent with the idea that certain members of this set are the progeny of one or two lymphocytes. Because of this potential clonal relationship, we can reach several conclusions about the diversity observed among these kappa light chains: (i) the diversity is due to somatic mutation, (ii) somatic mutations occur sequentially and accumulate in the first complementarity-determining region, and (iii) the extent of somatic variation in this sample is high, suggesting a somatic mutation rate of about 10(-3) per base pair per generation.

Amino Acid Sequence↗
PubMed1984

[Bilateral wrist joint arthrosis in a figure skater].

Aetiology and pathogenesis in the development of arthrosis are important problems in orthopedics. Micro-accidents as a result of excessive strain in sports are one of the reasons. The authors report a patient with arthrosis of both wrists. In former times he was a figure-skater (pairs-skating) for twelve years.

Athletic Injuries↗
PubMed1983

Aberrant rearrangement of the kappa light-chain locus involving the heavy-chain locus and chromosome 15 in a mouse plasmacytoma.

The creation of a functional antibody gene requires the precise recombination of gene segments initially separated on the chromosome. Frequently errors occur in the process, resulting in the formation of a non-functional gene. The non-functional genes can be generated by incomplete rearrangements, frameshifts, or the use of pseudo V or J joining segments. It is likely that these aberrant rearrangements arise by the same mechanism as is used in generating functional genes, a process which we have suggested may involve unequal sister chromatid exchange. Aberrant rearrangements of immunoglobulin genes occur in normal lymphocytes and play a major part in allelic exclusion. However, it has recently been suggested that aberrant rearrangements involving immunoglobulin and non-immunoglobulin genes may be involved in tumorigenesis. This suggestion has been stimulated by the frequent occurrence of translocations involving chromosomes known to carry immunoglobulin genes in B-cell malignancies. The rearrangement of non-immunoglobulin DNA to the heavy-chain locus has recently been reported. Some aberrant rearrangements of the kappa locus appear to be due to rearrangements to sites that do not include the conventional sequence for V gene segment joining. Here we describe an aberrant kappa rearrangement that has led to the joining of DNA from chromosomes 15, 6 and 12, and so appears to be the result of chromosomal translocations or transpositions. As 15/6 or 15/12 translocations have frequently been found in mouse plasmacytomas (as have analogous translocations in human lymphocyte tumours) this aberrant kappa rearrangement may be unique to the plasmacytoma from which it was isolated.

Animals↗
PubMed1982

Amplification of immunoglobulin lambda constant genes in populations of wild mice.

The lambda immunoglobulin light chain (Ig lambda) locus of BALB/c inbred mice consists of two variable region gene segments (V lambda)1-3, and four constant region gene segments (C lambda)1,2,4,5. Each C lambda gene segment is associated with a unique joining segment (J lambda)2,4-7, and they are organized in two paired units, J3C3-J1C1 and J2C2-J4C4 (refs 4, 8). Using cDNA probes specific for C lambda 1 and C lambda 2 (ref. 9) we have analysed the genomic organization of the C lambda gene segments in wild-derived and inbred strains of mice. Although Southern blots of the genomic DNA of inbred mice show a constant pattern of hybridization, wild-derived mice show a high degree of variation in the number, size and intensity of hybridizing fragments. We have now found that, per haploid genome, mice of a Mus musculus musculus stock isolated from Sladeckovce, Czechoslovakia (CzII) have at least 12 C lambda segments, and mice of a Mus musculus domesticus stock 'Centreville Lights' from Centreville, Maryland (CL) have at least 8 C lambda segments. There appears to have been relatively recent amplifications of the C lambda gene segments in wild mice.

Animals↗
PubMed1982

Independent segregation of NZB immune abnormalities in NZB x C58 recombinant inbred mice.

The study of NZB x C58 recombinant inbred mouse strains has revealed independent segregation of naturally occurring thymocytotoxic antibody and Coombs' anti-erythrocyte autoantibody. The lack of concordance of either of these autoantibodies with known heavy and light chain markers suggests that the autoantibodies are produced as a result of regulatory gene defects rather than alterations of antibody structural genes. Further, lack of concordance of the various autoimmune traits with each other or with H-2 or virus expression suggests that the autoimmune phenotype is not the result of a single "autoimmunity' gene but rather the outcome of faulty regulation of a number of independently segregating genes.

Aging↗
PubMed1982

DNA between variable and joining gene segments of immunoglobulin kappa light chain is frequently retained in cells that rearrange the kappa locus.

A systematic analysis of the fate of the DNA between kappa chain variable (V kappa) and joining (J kappa) genes in cells that have rearranged kappa loci was carried out. The DNA from a variety of kappa-producing plasmacytomas, lambda-producing hybridomas, and kappa-expressing lymphocytes was digested, fractionated by size, and analyzed with two probes containing sequences 5' of J kappa. In 13 of 28 plasmacytomas examined the rearrangement of V kappa and J kappa appears to be accompanied by loss of DNA upstream of J kappa. However, in the rest of the plasmacytomas one or more upstream sequences are retained in a new context. In 9 of 12 lambda-producing hybridomas (which frequently rearrange both kappa loci) one or more upstream segments were detected. These unique fragments were probably generated by a recombination event near or at the J kappa region. The extent to which the region between V and J is maintained in kappa-expression lymphocytes was also measured. Most (76%) of the region upstream of J kappa is retained in the population, even though 68% of the kappa loci are rearranged. In order to explain how these upstream elements occur in some, but not all, cell lines, and the significant occurrence in the lymphocyte population, we propose a model in which a step in V--J joining involves mitotic recombination by unequal sister chromatid exchange.

Alleles↗
PubMed1981

Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes.

A putative diversity segment of immunoglobulin heavy-chain genes (D segments) has been identified 700 base pairs 5' to JH1 DNA on the germ-line genome of the mouse. This 10-base pair D segment is flanked by two sets of sequences related to (SEE FORMULAR IN TEXT) which are possible recognition sites for a recombinase. The spacer separating the heptamer and the nonamer is 12 base pairs long on both sides of the D segment. As the space separating the two signal sequences in VH DNAs and JH DNAs is 23 +/- 1 base pairs long, the two recombinations required for creation of a complete immunoglobulin VH gene, a VH--D joining and a D--JH joining, follow a 12/23-base pair spacer rule. Allelic exclusion is discussed with respect to D segments.

Alleles↗
PubMed1981

Transcription of the unrearranged mouse C kappa locus: sequence of the initiation region and comparison of activity with a rearranged V kappa-C kappa gene.

In cells of the B-lymphocyte lineage, 8.4 kb transcripts are constitutively produced from unrearranged kappa constant region (kappa 0) loci. To help elucidate the molecular basis of this phenomenon, we have determined the nucleotide sequence surrounding the site of transcriptional initiation. The kappa 0 transcripts are initiated within a unique Eco RI fragment located about 8 kb upstream from the C kappa gene. The start site is about 36 nucleotides downstream from a Hogness consensus sequence (TGTAAAT) and nearly 200 nucleotides upstream from a sequence that is similar to those encoding the signal peptides of kappa light chains. These features, which are usually found in the 5' flanking regions of kappa variable region genes, suggest that the kappa 0 initiation sequence may be an evolutionary relic of some common ancestral 5' element. In contrast, there is no discernible V kappa-encoding element in 780 nucleotides of sequence downstream from the initiation site. From pulse-chase-labeling experiments with a pre-B-cell hybridoma line and direct measurements of transcriptional activity in isolated nuclei, we have estimated that the rate of transcription of the kappa 0 locus is significantly lower than that of a rearranged V kappa-C kappa gene. This result, together with the fact that unrearranged V kappa genes are transcriptionally silent, suggests that structural features of both the V kappa and C kappa loci contribute to the overall transcriptional efficiency of a rearranged V kappa-C kappa gene. The 8.4 kb transcripts are not processed into any stable RNA products, despite the fact that they contain some apparently normal splice junctions; rather, they are degraded within the nucleus at about half the rate with which a kappa mRNA precursor is processed. Conceivably, the transcriptional activity of the kappa 0 locus might be a prerequisite for its recombinatorial activity.

Amino Acid Sequence↗
PubMed1981

[Breaking-out of osteosynthesis plate following femoral osteotomy near the hip joint (author's transl)].

Despite the progress in arthroplasty (TEP, double-cup plasty, ceramic prosthesis), adjustment osteotomy at the femur for prevention and treatment of osteoarthrosis of the hip is still an important procedure. It aims at reducing or removing pre-arthrotic deformity or at utilising remaining cartilaginous zones for taking part of the load. A wedge-shaped excision is usually performed in the intratrochanteric area. The fragments are then osteosynthesized under pressure by means of a blade plate (1, 2, 3, 4). If the osseous bridge between the blade and the osteotomy surface is too narrow, the blade may break out from its position. In such cases reosteosynthesis with a 90 degrees plate will not produce a stable result. The article describes three possibilities of saving the situation in such emergencies.

Adult↗
PubMed1980

The joining of V and J gene segments creates antibody diversity.

The variable regions of mouse kappa (kappa) chains are coded for by multiple variable (V) gene segments and multiple joining (J) gene segments. The V kappa gene segments code for residues 1 to 95; the J kappa gene segments code for residues 96 to 108 (refs 1-3). This gene organisation is similar to that encoding the V lambda regions. Diversity in V kappa regions arises from several sources: (1) there are multiple germ-line V kappa gene segments and J kappa gene segments; (2) combinatorial joining of V kappa gene segments with different germline J kappa gene segments; and possibly, (3) somatic point mutation, as postulated for V lambda gene segments. Also, from a comparison of the number of germ-line J kappa gene segments and amino acid sequences, it has been suggested that J kappa region sequences may be determined by the way V kappa and J kappa gene segments are joined. This report supports this model by directly associating various J kappa sequences with given J kappa gene segments.

Animals↗