ALBERT

Notizen: Two antigenically distinct populations of b-negative light chains have been identified in the serum of two b locus homozygous rabbits undergoing total b locus suppression. Whilst one population of molecules is readily detected in all rabbit sera and represents the previously described lambda chain, a second and minor population of b-negative molecules is detected which is readily detected in normal rabbit serum only rarely. Thus, it appears that it is not specificities of the c7-, c-21 system that are being detected but rather a previously unrecognized allotypic system or the products of a different light chain locus.

Notizen: Two genetically inbred strains of rats with new histocompatibility alleles—the KGH and WKA strains—were characterized. Neither the KGH nor WKA strain cells reacted with known Ag-B * specific antisera; specific antisera against these strains did not react with cells from any known Ag-B group; and there was no cross-reactivity between the histocompatibility antigens of the two strains. On the basis of these data, the KGH strain was assigned the Ag-B7 allele and the WKA strain, the Ag-B8 allele. Both strains were low responders to the test antigen poly(Glu52Lys33Tyr15). In various crosses, the antibody response segregated as expected, i.e. low response was associated with the Ag-B7 or Ag-B8 alleles in the F2 and backcross generations.

Notizen: The relationship between the mixed leukocyte reaction (MLR) and the serologically defined antigens of the major histocompatibility complex was examined in twenty-three strains of genetically inbred rats. Interstrain cell combinations involving representative members of the different major Ag-B groups were associated with significant MLR responses. Strain combinations within a single Ag-B group were never associated with significant MLR responses, suggesting that non-Ag-B loci probably do not play an important role in MLR reactivity among inbred strains of rats. The WKA and KGH strains, representing newly defined histocompatibility groups, were also examined. The WKA strain (Ag-B8) showed positive MLR responses against representative members of all the different Ag-B groups, including the KGH strain. The KGH strain (Ag-B7) had positive MLR responses against all Ag-B groups except Ag-B1: no reactions occurred with three strains in this group, and inconsistent and weak reactivity was observed with a fourth strain (F344).

Notizen: The amino acid sequence near the N-terminus of a human immunoglobulin (Ig) light (L) chain has been determined. This sequence is more homologous to avian Ig L chains than to human Ig L chains, and defines an additional variable (V-) region subgroup designated as VλVI. These data also suggest that all vertebrates share large numbers of Ig V-region genes and that 'species-specific’residues reflect the expression in different species of different sets of V-region genes. Control at a level equivalent to ‘regulatory genes’* determines which genes are expressed. Our findings raise a question concerning the possible role of redundant DNA, in that at least some of the ‘nonsense’ DNA in one species may actually be 'sense’DNA in another. We hypothesize that in evolution‘gene expansion’is a regular mechanism for the generation of new genes and that different members of a given group of repetitious genes are expressed in different species. Such a phenomenon is basically similar to the‘mechanism’controlling the differential expression of genes during embryonic differentiation. Our hypothesis differs from the previous version of the germ-line hypothesis proposed for genetic control of antibody variability which involves ‘sudden excessive gene expansion and contraction’. Evidence suggesting that the‘gene expansion’mechanism may also be applicable to a lesser degree to other gene systems is briefly reviewed and discussed.

Notizen: Stepwise incubation with specific H-2 antibody and rabbit-anti-mouse Ig was used to modulate the expression of selected H-2 specificities on the surface of lymph node cells or EL 4 leukaemia cells. Modulation was reflected in a loss of sensitivity to complement-dependent lysis and a polar pattern of immunofluorescence (‘capping’). Specificity H-2.5 on H-2a cells was co-modulated with H-2.11 and so was H-2.11 with H-2.5 on H-2k cells. However, when H-2.11 on H-2k cells was modulated, the cells did not loose cytotoxic sensitivity for H-2.5. This asymmetry in co-modulation of H-2.5 and H-2.11 may be accommodated by the duplication model of the H-2 complex which postulates a double determination of H-2.5 in the H-2k (unlike H-2a) chromosome, with one determinant being in the K region (where also the H-2.11 determinant is located) and the other in H-2D. The modulation results with H-2.5 and H-2.11 are compatible with the view that various H-2K specificities may represent distinct antigenic sites on the same glycoprotein molecule whereas H-2D specificities are on separate molecule(s). The independent modulation of H-2D.4 and H-2K.11 specificities further indicates that molecules of the two classes are also secondarily not linked in the membrane structure. Modulation-induced cytotoxicity resistance was further shown to persist even when the specific H-2 antibody is newly added; this suggests that it is a change in the distribution of the H-2 antigen to be held responsible (rather than the loss of the sensitizing antibody).A modulated expression of a certain H-2 specificity might then be expected to affect its blocking relationship to another H-2 specificity; the blocking index expresses the degree of interference by antibody attached to one of them with the attachment of antibody to the other. The blocking relationship between H-2.4 and H-2.11 was shown to be completely abolished by the independent modulation of H-2.11. In contrast to this, the blocking index for H-2.5 and H-2.11 remained practically constant following the modulation of either specificity; this indicates that the intramolecular configuration of such two H-2 sites may not be altered by the gross redistribution of the whole molecule in the plane of the membrane. The rigidity of this configuration seems to be maintained by neuraminidase-sensitive groups as suggested by the reduced blocking index in neuraminidase pretreated cell.

Notizen: The effects of varying degrees of multiparity on placental and foetal weights were examined in BALB/c female mice pregnant by either BALB/c or C3H males. Continual decreases in placental weights are observed through third pregnancies followed by progressive increases in both syngeneic and allogeneic placentas. In syngeneic pregnancies, foetal weights are generally proportional to placental weights, but those of allogeneic pregnancies tend to oppose placental weights. Evidence is presented that placental weights are also influenced by foetus-specific antigens and the genotype of previous litters. In this strain combination, placental weights reflect changes in maternal reactivity different from those previously reported with tumour allografts.

Notizen: The Ag system, inherited antigenic determinants on serum low density lipoprotein and Australia antigen (Au), an antigen associated with an infectious agent which can cause hepatitis in man were discovered by reacting in immunodiffusion tests sera from multiply transfused patients and sera from geographically human populations. The approach has been pursued in the experiments described herein and has resulted in the identification of seventeen precipitating systems. They are different from the previously described anti-Au and anti-Ag precipitins. In some cases they may be confused with Australia antigen precipitins, and care should be taken in the evaluation of Au test systems where comparisons with antigen controls are not routinely performed.

Notizen: Book Review in this Article. Einfiihrung in die Immungenetik, Grundlagen der Modernen Genetik 9, KLAUSDIETER BAUER

Notizen: A new type of Gm genetic marker combination in an IgG1 immunoglobulin, Gm(z) together with a non-a marker, is here described. This indicates the presence of a new gene, Gmz,non-a, which most likely originated on the basis of an intragenic recombination at the IgG1 cistron. Immunochemical and immunogenetic studies showed that no other IgG1 Gm markers were expressed by the unusual gene, and there was no evidence for deletions or duplications at the IgG1 cistron.

Notizen: The cell mediated lympholysis (CML) test is normally carried out in 2 steps–first, the lymphoid cells are allowed to interact in mixed allo-culture (MLC) and secondly, they are reacted against chromium labelled phytohaemagglutinin transformed lymphoblast cells, carrying the appropriate target allo-determinants. The genetic control of target structures has already been localized to the H-2D and H-2K regions of the H-2 gene complex, but the genetic basis of the generation of effector capacity is not understood and is the subject of this report; the suggestion that there is a separate genetic basis came from the observation that H-2D and/or H-2K region incompatibility alone was insufficient for CML to occur and that incompatibility at the Ir-Ss-Slp regions of the H-2 complex was also required. In the Ir region also reside the genetic control for the strong lymphocyte activating determinants (LAD) of the H-2 gene complex and it was thought possible that they might also be responsible for activating the effector cells for CML.The genetic experiments were done with congenic resistant and recombinant mouse strains, so it was possible to study in relative isolation, and in selected combinations which of the various defined regions of the H-2 gene complex control the initiation of effector capacity in CML.Five day,‘one-way’(parent-F1) mixed lymphocyte cultures–incompatible only for defined regions of the H-2 gene complex were reacted with 51Cr-labelled PHA blast cells and the specific chromium release was calculated.The results give evidence for a separate but closely linked genetic control for the effector cell stimulating (ECS) and LAD functions. The ECS genes map between the LAD and Ss-Slp genes of the H-2 complex.