Cooperation between Carrier-reactive and Hapten-sensitive Cells <Emphasis Type="Italic">in vitro</Emphasis>

THE mechanism, known as the carrier effect, whereby immunity to one or more determinant groups enhances the response to other determinants on the same multivalent antigen, was first recognized in delayed hypersensitivity to haptens, in which, for an appreciable response, the hapten must be coupled to the same protein carrier for priming and challenge^{1, 2}. Carrier specificity has also been demonstrated in the secondary antibody responses to hapten protein conjugates³. Two alternative hypotheses have been advanced to explain this specificity. The “local environment” hypothesis supposes that the hapten-sensitive cell recognizes both the hapten and the carrier determinants. However, the antihapten antibodies produced do not distinguish details of the carrier molecule and so do not reflect the specificity of the cellular receptor. Furthermore, inert spacer molecules inserted between hapten and carrier do not interfere with carrier specificity in the antibody response³. Reflecting current views on the cooperation between thymus-derived (T) and bone marrow derived (B) lymphocytes in the antibody response to various antigens⁴, the second hypothesis invokes two or more cells, one with receptors directed towards the hapten (hapten-sensitive cell), the others specific for the carrier molecule proper (carrier-reactive cells). Supporting this is the observation that pre-immunization to a particular protein carrier alone could potentiate the primary or secondary antihapten response to a hapten conjugated to that protein⁵. In an adoptive transfer system, moreover, the efficiency of antihapten antibody production by cells primed to a particular hapten-protein conjugate and stimulated with the hapten conjugated on a heterologous protein, is significantly enhanced by the introduction of cells primed to the heterologous carrier alone. Anti-carrier serum antibody does not cause such enhancement⁶. The carrier-reactive cells must therefore cooperate in increasing the efficiency of the hapten-sensitive cells in some way other than by providing humoral anti-carrier antibody. Recent work strongly suggests that carrier reactive cells are thymus-derived^{6, 7}.     

Function of the <Emphasis Type="Italic">rel</Emphasis> Gene in <Emphasis Type="Italic">Escherichia coli</Emphasis>

Sokawa et al. suggest that rel^- strains of Escherichia coli possess abnormal protein synthesizing machinery, which cannot carry out normal protein synthesis when the supply of amino-acids is limited.     

“Pleiotypic Response”

A hypothesis has been developed to relate stringent control in bacteria to a set of interactions involved in the regulation of growth of transformed and untransformed mammalian cells.     

Electrotonically Coupled Interneurones produce Two Types of Inhibition in <Emphasis Type="Italic">Aplysia</Emphasis> Neurones

IN the abdominal ganglion of Aplysia californica, there are two types of inhibitory post-synaptic potentials (IPSPs). There are unitary short-lasting IPSPs which occur as the result of conductance changes during the movement of Cl^? across the synaptic membrane—IPSPs which have definite equilibrium potentials and characteristics similar to those described for other neuronal systems¹—and there are IPSPs which last much longer and may be much more effective in regulating the activity of the neurone, which Taue has called “inhibitions of long duration” (ILD)^2,3. In Aplysia some of these long lasting inhibitory potentials are produced by conductance changes and have definite equilibrium potentials⁴. Long lasting inhibitions or “slow inhibitory potentials” as well as short lasting IPSPs have also been described in vertebrate sympathetic ganglia⁵, but in these, long lasting IPSPs are not accompanied by changes in membrane conductance. Some of the long lasting inhibitions (LLI) have been explained on the basis of an ATP-dependent electrogenic Na+ pump⁶. Presumably this ATP-dependent pump hyperpolarizes the membrane by causing an outflux of Na+ from the cell which is more rapid than the corresponding “active” influx of K+⁷. There is evidence now for the existence of such an electrogenic Na+ pump in some of the identified neurones of the abdominal ganglion of Aplysia californica⁸. Pinsker and Kandel⁹ have found some evidence that in these neurones the electrogenic Na+ pump is activated by the synaptic action of an identified cholinergic inhibitory interneurone, L10, producing the long lasting “late IPSP”. But Kehoe and Ascher¹⁰, although agreeing that the same interneurone (L10) produces both types of IPSPs in the follower neurones, have shown that the “late IPSP”⁹ is due to an increase in the K+ conductance and that it has an equilibrium potential around ?90 mV. I have found that in this abdominal ganglion there is another specific interneurone which is electrotonically coupled to L10 and which, when activated, produces a long lasting inhibition (LLI) in a number of follower neurones. Thus L10 produces the LLI or “late IPSP” in some follower neurones not directly, but through the mediation of another interneurone.     

Inhibition of DNA Synthesis but not of Poly-dAT Synthesis by the Arabinose Analogue of Cytidine <Emphasis Type="Italic">in vitro</Emphasis>

Kimball and Wilson¹ reported that the arabinose analogue of cytidine (ara-C) inhibited DNA polymerase in a crude extract prepared from Ehrlich ascites cells. Furth and Cohen² observed cytosine arabinoside triphosphate (ara-CTP) inhibited DNA polymerase in extracts from either calf thymus or bovine lymphosarcoma tissue, although these investigators³ had already found no effect of ara-CTP on DNA polymerase from Escherichia coli. The inhibition in both of these cases could be substantially reversed by dCTP; but incorporation of the arabinose nucleotide (ara-CMP) into DNA could not be unequivocally demonstrated. Graham and Whitmore⁴ reported the incorporation of ara-C into DNA in vivo and the inhibition of a DNA polymerase from L cells by ara-CTP. They found that ara-CMP was initially incorporated into small DNA strands but subsequently appeared in long strands. Momparler⁵ has presented evidence that, in vitro, ara-C incorporation was limited to the 3′-hydroxyl end of DNA chains. Such incorporation might be expected to block further chain elongation but this expectation was not supported by the evidence presented by Graham and Whitmore.     

Endopeptidase Activity of Phage λ-Endolysin

JACOB and Fuerst^1,2 demonstrated the presence of a bacteriolytic enzyme (λ-endolysin) in the induced cultures of lysogenic Escherichia coli K12 (λ). The enzyme was later identified as the product of gene R; of phage λ³ which is involved in bacterial lysis at the end of a latent period. The enzyme is apt to form spheroplast-like structures in E. coli² and one would therefore expect its substrate to be murein.     

Induced Bivalent Interlocking and the Course of Meiotic Chromosome Synapsis

WHEN chromosomes pair at meiosis the bivalents so formed do not normally interlock. Heat-treatments can, however, induce bivalent interlocking in the locust Locusta migratoria. Only the longest bivalents interlock and usually only two are found per cell; two “rod” bivalents, with single chiasmata, two “ring” bivalents, each with two or three chiasmata, or one “rod” and one “ring” bivalent (Fig. 1a, b and c). The nature of this interlocking and the metaphase orientational and congressional properties of interlocked bivalents are analysed in detail elsewhere¹.     

Inhibition of Transformation of Bacillus subtilis by Heavy Metals

Mercuric ions, as well as organomercuric ions and cadmium ions, can inhibit deoxyribonucleic acid-mediated transformation in Bacillus subtilis 168 without decreasing the viability of the total population. Differences in the inhibition of transformation by mercuric ions are identifiable on a temporal and concentration dependence basis. Sensitivity to low concentrations (9.2 x 10(-8) M) appears early in the uptake of deoxyribonucleic acid before the transformed markers have become insensitive to deoxyribonuclease. Resistance to "low concentrations" of Hg(2+) is kinetically indistinguishable from the requirement for magnesium in the transformation process. This inactivation is not reversed by the mercury-binding compound glutathione. Sensitivity to mercuric ions at a higher concentration (5.52 x 10(-7) M) occurs after the donor deoxyribonucleic acid has become insensitive to deoxyribonuclease. These complex interactions between mercuric ions and the process of transformation are discussed.     

Polyamine Limitation of Growth Slows the Rate of Polypeptide Chain Elongation in Escherichia coli

The rate of polypeptide chain elongation during steady-state, polyamine-limited growth of a mutant of Escherichia coli was measured by two independent techniques. Analysis of polysome patterns gave values of 17.5 and 9.5 amino acids per s at 37 C in unstarved and polyamine-limited cells, respectively. From the kinetics of entry of labeled amino acids into polypeptides of defined molecular weights, values at 30 C of 10.1 and 5.8 amino acids per s were obtained for unstarved and polyamine-limited cultures, respectively. Correction of these values to 37 C resulted in rates of 15.0 and 8.7 amino acids per s. These results support the previous conclusion, based on the kinetics of beta-galactosidase induction, that polyamine starvation decreases the rate of protein synthesis by limiting the velocity of polypeptide chain elongation.