Biological and serological comparison of syngeneic and allogeneic anti-idiotypic antibodies.
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Biomedical subjects
Publications and source records attributed to E Weiler.
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Baseline EMG measures of general laryngeal area muscle tension while speaking and during silence were taken from a group of 21 normal subjects and 7 subjects diagnosed through indirect laryngoscopy as having vocal nodules. In an attempt to reduce their baseline scores, the vocal nodule patients underwent 8 EMG biofeedback training sessions followed by a 2-week follow-up session. Sophisticated listeners then judged the qualities of the voices produced during the base-line and follow-up sessions. Measures of sound pressure levels for the speech samples were also taken to determine their effects on EMG scores. Results of the statistical analyses revealed that significant differences in general laryngeal area muscle tension while speaking and in silence exist between normal and pathological subjects; and that subjects with vocal nodules could significantly reduce these tension levels with EMG biofeedback training. A positive correlation was then found between the EMG measures and the judgments of voice qualities. No correlations were found between EMG measures and sound pressure levels.
Twelve normal hearing awake adult subjects were tested to determine the minimum intensities of white noise which produce a detectable change in digital blood flow. A digital plethysmograph was utilised to detect and record these changes. The stimulus intensity was adjusted in 5 dB increments, beginning at an intensity below voluntary threshold, for a total of four data trials. The range of minimum intensities producing the response was 20 to 60 dB HTL, however, there was no significant variation in the mean intensities required to produce the response from trial to trial (F = 0.48, df-3.30, N.S.). The results support further research into the development of peripheral vascular techniques in determining the presence or absence of hearing for individuals who cannot be tested by voluntary audiometry.
In BALB/c mice, antibodies to the alpha-(1-3) glucosidic linkage of some dextrans (Dex) carry the idiotype of the BALB/c myeloma protein J558. Both specific antibody and idiotype are inherited in a dominant fashion, linked to the immunoglobulin (Ig) (heavy chain) allotype Igla of BALB/c mice (Eur. J. Immunol. 1975. 5: 775). In F1 hybrid mice from the parent strains SJL and BALB/c, we were able to suppress the expression of anti-Dex antibodies by immunizing prospective SJL mothers to the J558 idiotype. The state of suppression in the progeny was ascertained by immunization with Dex, and tests for the following were carried out: (a) antibodies specific for Dex; (b) inhibition of such antibodies (if present) by antiidiotypic serum to protein J558; (c) presence of the J558 idiotype; and (d) concentration of lambda1 chains (which are associated with the 558 idiotype) in the serum. SJL mothers, once immunized, conferred suppression upon several successive litters, spanning a period of 4-5 months. Suppression in F1 progeny animals lasted for 16 weeks or more. Spleen cells from suppressed F1 mice which had neither been treated with Dex nor with J558 protein, were able to confer suppression to further F1 newborn mice.
BALB/c mice were immunized against the idiotype of BALB/c myeloma J55,. Syngeneic, specific anti-idiotypic antibodies against this germ line idiotype were shown by the isoelectric focusing technique to be markedly heterogeneous. In fact, the heterogeneity of isogeneic anti-idiotypic sera appeared to be comparable to those of allogeneic anti-J558 sera, raised in A/J and CB20 mice. As a rule, individual mice exhibit different clonal spectra. By spleen cell transfer experiments, each individual spectrum of clones could be expanded in order to arrive at an estimate of the size of anti-idiotypic repertoires. These were found to be of the order of 7-16 different anti-idiotypic clones for an individual BALB/c mouse. From the infrequency of clonal repetition we conclude that the repertoire of the BALB/c strain must be well in excess of one hundred anti-idiotypic molecular species.
Postnatal serum concentrations of IgG2a of paternal allotype, measured in congenitally thymusless nude mice, increase with kinetics and titers comparable to their normal congeneic counterparts. Lipid A, the mitogenic part of LPS, stimulates IgG synthesis in nude mice when it is given 7 days after birth. IgG concentrations at 15 days of age are 6- to 8-fold higher than in untreated control nudes; this is considerably lower, however, than in normal mice, which show up to 45-fold higher IgG2ab levels after lipid A treatment. A thymus graft from nearly congeneic donors of the same age, transplanted at 4 days after birth, also stimulates long-lasting IgG synthesis in the nude recipients. If the grafted nudes are injected with lipid A 3 days later, IgG synthesis is further stimulated 8- to 16-fold. The data are discussed in relation to the thymus dependency of IgG production and the conditions for lipid A stimulation.
Allotypically marked antisera to the hapten oligo-D-alanine were studied over periods up to 10 months in individual mice and in serial transfers of both nonimmune and memory cells to irradiated recipients. Parameters observed were divalent association rate constants, affinity and autoradiography of isoelectric focusing (IEF) spectra. The two allotypic subpopulations of heterozygous mice are shown to be independent with respect to affinity. Association rate constant, affinity, and IEF spectra of the antibody populations remain largely stable in most mice over prolonged periods. There is an occasional isolated dramatic change in a single property of one allotypic subpopulation; this may be in the direction of either lower or higher rate constant or affinity. While different recipients of naive spleen cells from a single donor, when immunized, differ one from the other in the measured antibody properties, the characteristics now established in each recipient persist in a lineage of transferred memory cells up to 4 generations, with infrequent changes in isolated properties of only one allotypic subpopulation. The limited changes observed would be in agreement with a model of moderate somatic variability superimposed on a small spectrum of germ line genes.
Spleen cells from BALB/c or BALB-Igb mice immunized against the determinant oligo-D-alanine were transferred to the following recipients: normal BALB/c; lethally irradiated BALB/c; and congenitally athymic BALB/c-nu. Irradiated as well as nude recipients permitted the development of a strong adoptive antibody response, while the response in normal BALB/c recipients was very low ("isogeneic barrier"). Using allotypically marked spleen cells from BALB-Igb donors it was shown that the antibodies in irradiated as well as in nude recipients were produced by donor cells. The same conclusion was drawn by assessing isoelectric focusing spectra, which in each transfer displayed the individually characteristic pattern of the donor. In addition to specific antibodies, the donor cells produced considerable levels of IgG, as characterized by allotype, but again only in nude and in irradiated recipients. The ready permissiveness of nude recipients towards congenic memory cells could be abolished when prospective recipients were restored, some time prior to transfer, by BALB/c thymus or BALB/c spleen cells. The results are interpreted to suggest that the isogeneic barrier in normal recipients is due to a thymus-dependent suppression or rejection of memory cells by the recipients.
IgG of paternal allotype first becomes detectable in the serum of (BALB/c x C57BL/6)F(1) mice between day 12 and 14 after birth and reaches adult levels at an age of 5 wk. Since in mice there is a transfer of maternal IgG molecules through the placenta and via milk, F(1) heterozygous at the allotype locus were used and the concentrations of IgG with paternal allotype were measured. This was done by a sensitive method capable of detecting IgG concentrations as low as 5 x 10(-4) of normal adult serum levels. It is based on the quantitative inhibition of allotype-specific facilitation of hemolysis. When lipid A or Salmonella bacteria were injected into neonatal mice, a stimulation of IgG synthesis was observed. Thus IgG levels were enhanced 10-30-fold compared to the nontreated mice. No increase in IgG levels was obtained in adult mice after treatment with lipid A. Whether the newborns were injected at birth, on day 2, 4, or 7, IgG was first demonstrable in the treated mice at an age of 6-11 days. The increase in IgG levels was not paralleled by a demonstrable antibody activity against lipid A, SRBC, and LPS. Thus the bulk of newly induced IgG is probably a statistical distribution of different specificities.
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