Biomedical subjects

H Völk

Publications and source records attributed to H Völk.

5 recordsLinked to original sources

PubMed1998

Wide tissue distribution of axolotl class II molecules occurs independently of thyroxin.

Unlike most salamanders, the Mexican axolotl (Ambystoma mexicanum) fails to produce enough thyroxin to undergo anatomical metamorphosis, although a "cryptic metamorphosis" involving a change from fetal to adult hemoglobins has been described. To understand to what extent the development of the axolotl hemopoietic system is linked to anatomical metamorphosis, we examined the appearance and thyroxin dependence of class II molecules on thymus, blood, and spleen cells, using both flow cytometry and biosynthetic labeling followed by immunoprecipitation. Class II molecules are present on B cells as early as 7 weeks after hatching, the first time analyzed. At this time, most thymocytes, all T cells, and all erythrocytes lack class II molecules, but first thymocytes at 17 weeks, then T cells at 22 weeks, and finally erythrocytes at 26-27 weeks virtually all bear class II molecules. Class II molecules and adult hemoglobin appear at roughly the same time in erythrocytes. These data are most easily explained by populations of class II-negative cells being replaced by populations of class II-positive cells, and they show that the hemopoietic system matures at a variety of times unrelated to the increase of thyroxin that drives anatomical metamorphosis. We found that administration of thyroxin during axolotl ontogeny does not accelerate or otherwise affect the acquisition of class II molecules, nor does administration of drugs that inhibit thyroxin (sodium perchlorate, thiourea, methimazole, and 1-methyl imidazole) retard or abolish this acquisition, suggesting that the programs for anatomical metamorphosis and some aspects of hemopoietic development are entirely separate.

Ambystoma↗

PubMed1997

A protein binding specifically to the IgG2b switch region.

The Abelson-virus-transformed mouse pre-B-cell line 18-81 switches almost exclusively from mu to gamma 2b. From nuclear extracts of this cell line, we have isolated a factor that specifically binds to S gamma 2b. After an eight-step purification scheme, in which different types of DNA-affinity chromatography were used as key elements, we obtained a preparation with two narrowly spaced bands at approximately 69 kD on a silver-stained SDS gel. Binding specificity of main-peak fractions of affinity-purified proteins was analyzed by gel shift assays, in which S gamma 2b, but not S mu, competes. The results are consistent with this factor being part of the switch recombinase.

Animals↗

PubMed1995

A "minimal essential Mhc" and an "unrecognized Mhc": two extremes in selection for polymorphism.

The high polymorphism of classical Mhc molecules found in mammals is not simply the result of strong selection for pathogen resistance in the recent past, since there are virtually no examples of diseases caused by infectious pathogens for which resistance is determined by particular Mhc haplotypes, and in the best-studied case, a particular aspect of malaria in humans, the selection is remarkably weak. We discuss three possibilities to explain high polymorphism in mammals: accumulating, merging and boosting. The mammalian Mhc is complicated and redundant, so that every Mhc haplotype may give some level of resistance due to multiple classical Mhc genes as well as other disease resistance genes; this frustrates the attempts to demonstrate selection for disease resistance. We have looked at two vertebrate groups that may represent two extreme examples of selection for Mhc polymorphism. Birds, like mammals, have highly a polymorphic Mhc that determines strong allograft rejection. However, chickens have a much smaller, compact and simpler Mhc than mammals, as though the Mhc has been stripped down to the essentials during evolution. The selection on a single Mhc gene should be much stronger than on a large multigene family and, in fact, there are a number of viral diseases for which resistance and susceptibility are determined by particular chicken Mhc haplotypes. We have determined the peptide motifs for the chicken class I molecules from a number of haplotypes, which may explain some disease associations quite simply. On the other hand, salamanders have very low Mhc polymorphism and slow allograft rejection. We have isolated axolotl Mhc molecules and shown that they cosegregate with the locus that determines graft rejection in the axolotl, have only a few alleles and only weakly stimulate axolotl T lymphocytes in mixed lymphocyte culture. We believe that salamanders have classical Mhc molecules but most T cells do not recognize them, so that there is no strong selection for polymorphism.

Amino Acid Sequence↗

PubMed1993

Immunoglobulin class switch recombination.

A B lymphocyte that produces the immunoglobulin heavy (H) chain mu may switch to the production of another heavy chain class: gamma, epsilon, or alpha. Since the new heavy chain retains the original variable (V) region, antigenic specificity is maintained. The switch is accompanied by a large deletion of DNA at the heavy chain locus. To explain how this deletion is generated, three models have been proposed: recombination between homologs, unequal sister chromatid exchange, and looping out and deletion. While none of the predicted recombination products of the first two models have been found, both by-products of looping out--inversions and circular DNA--have been isolated. Thus looping out and deletion appears to be the appropriate model to explain the genetic events leading to the immunoglobulin heavy chain class switch. One requirement for switching may be transcription of the constant (C) region to which the cell switches. The switch rearrangement is catalyzed by a switch recombinase, and the isolation of the components of this putative enzyme system is in progress. Although the switch deletion is an accepted fact, the discussion is enlivened by scenarios for switching without DNA rearrangement; such suggestions include processing at the RNA level and trans-splicing.

Animals↗

PubMed1990

MHC-like molecules in some nonmammalian vertebrates can be detected by some cross-reactive monoclonal antibodies.

mAb to human and mouse MHC molecules were tested for binding to blood or spleen cells of various nonmammalian vertebrates by immunofluorescence and flow cytometry. Those that bound were used to immunoprecipitate cross-reactive molecules from biosynthetically or cell surface-labeled spleen or blood cells. In addition, mAb to human MHC molecules were screened by Western blots. As expected from the results with xenoantisera, there were few mAb that cross-reacted, and many of these cross-reactions were not specific for MHC-like molecules. Less than 10% of the mAb tested bound to the cells of any particular species, with very few positive for more than one species. Of those mAb that bound cells, many failed to precipitate any radioactive bands, and most bands precipitated were not recognizable as MHC-like molecules. Five mAb reacted with Xenopus class II, one of which also immunoprecipitated axolotl class II. Another of these reacted with a candidate for class II in the lamprey, but this molecule had features unlike those expected for mammalian class II molecules. Four other mAb reacted with candidate molecules. in the trout and shark. None of the mouse alloantibodies immunoprecipitated nonmammalian vertebrate MHC-like molecules. In contrast to the results with most xenoantisera, the mAb cross-reacting with amphibian class II molecules recognized a number of different linear epitopes on the surface of the polymorphic non-Ig beta 1 domain of class II molecules. Few mAb recognized bands in Western blots of nonmammalian vertebrate cells and the candidate molecules from fish had features different from known mammalian MHC molecules.

Amphibians↗