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J M Teale

Publications and source records attributed to J M Teale.

68 records · Page 4Linked to original sources
PubMed1980

Tolerance as an active process.

The clonal deletion model proposed by Burnet and Lederberg and expanded by Nossal was one of the first theories concerning the nature of tolerance of self constituents. The model proposed that during the maturation of lymphocytes into immunocompetent cells, there is a sensitive differentiation stage whereby contact wth antigen results in specific inactivation of the cell. Experimental evidence indicates that neonatal or immature B lymphocytes are indeed different from adult lymphocytes in their extreme sensitivity to tolerance induction even at low antigen concentrations and with antigens that are normally immunogenic. The present study examines the mechanism of this tolerance phenomenon by determining whether or not tolerance of immature B cells is an active process and what specific interactions can induce this event. We used various putative inhibitors of tolerance induction in the splenic focus assay which examines the tolerance susceptibility of individual B cells. The results suggest that tolerance requires protein synthesis and that this process is initiated only after a minimum threshold affinity of binding occurs between antigen and cell-surface receptor with subsequent receptor interlinkage.

Animals↗
PubMed1980

Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system.

The maturation of B-lymphocyte function during fetal development was studied in vivo and in an in vitro organ culture system. The results indicated that the progenitors for 2,4-dinitrophenol (DNP)-specific B cells are present as early as 14 d of gestation in liver and possibly as early as 15 d in spleen. In addition, it was found that the organ culture system supports the development of B lymphocytes as measured by an increase in both the percentage of surface immunoglobulin-positive cells and the frequency of clonable DNP-specific B cells after culturing. The majority of anti-DNP-secreting clones resulting from the antigenic stimulation of fetal B cells produced only the IgM isotype, and the ability to secrete the IgG isotypes increased as a function of gestational age. Because fetal DNP precursors from spleens and livers that had been incubated in organ culture resulted in a greater proportion of clones secreting IgG compared with age-matched uncultured controls, it was concluded that the maturation with regard to the ability to secrete IgG can occur in vitro. In studies relating to the ontogenetic development of tolerance susceptibility, it was found that up to one-half of the DNP-specific B-cell precursors from livers and spleens less than 18 or 19 d of gestation were resistant to tolerogen treatment for 24 h as if in a pretolerant phase. However, if tolerogen were present for 3--5 d during organ culture there was near total elimination of potential DNP clones. This finding suggested that the 24-h induction period was insufficient for affecting the DNP-specific precursors in livers and spleens from the earlier gestational ages, and that a proportion of precursors could subsequently form DNP clones in the splenic focus assay after the removal of tolerogen.

Animals↗
PubMed1979

Autoimmune disease and the theory of clonal abortion. Is it still relevant?

Explanations for self-tolerance and its failure in autoimmune disease remain conjectural. Earlier deletional theories and the later clonal abortion theory as a basis for central B-cell (and possibly T-cell) tolerance seemed to conflict with various experimental and clinical observations, including those relating to the ability to induce autoimmune reactivity in normal adult animals. Accordingly, immunoregulatory controls have dominated discussions. However, there is recent compelling experimental evidence in favour of clonal abortion of B lymphocytes in the absence of T-cell help. It is proposed that two sets of regulatory systems operate at different stages in life to establish and maintain self-recognition: a central tolerance operates through clonal abortion during embryonic and early postnatal life and during childhood and beyond, ancillary regulatory systems deal with the self-reactive cells which emerge in a milieu in which helper influences interfere with clonal abortion.

Adult↗
PubMed1979

In vitro model for natural tolerance to self-antigens. Inhibition of the development of surface-immunoglobulin-negative lymphocytes into T-dependent responsive B cells by antigen.

Neonatal and adult splenic cell suspensions were labeled with fluorescein isothiocynate-anti-Ig and fractionated into surface-immunoglobulin- (s-Ig) positive and s-Ig-negative subpopulations by the fluorescence-activated cell sorter. The subpopulations were then tested by splenic focus assay for both frequency and tolerance susceptibility of clonable 2,4,-dinitrophenol (DNP) precursors. It was shown that both adult, and neonatal, s-Ig-negative subsets contained clonable DNP-specific B-cell precursors. However, because these precursors result in fewer clones secreting IgG, they appeared to be less mature than the s-Ig-positive precursors. In the absence of helper T cells, it was found that exposure of s-Ig-negative lymphocytes to tolerogen during the process in which they were acquiring surface receptors resulted in nearly total abrogation of potential DNP clones. This finding provides compelling evidence for clonal abortion.

Animals↗
PubMed1978

The antigenic structure of bovine serum albumin. Evidence for multiple, different, domain-specific antigenic determinants.

Using antiserum to native bovine albumin and antigenically active fragments of the protein, we have isolated antibodies directed to each of the three domains and to several subdomains of the albumin molecule. Using albumin and these fragments as inhibitors of the reaction between 125I-albumin and any given antibody population, we have demonstrated that: (a) each domain of albumin is antigenically distinct from each of the other domains; (b) each domain possesses a minimum of two different antigenic determinants; and (c) the entire albumin molecule possesses a minimum of six different, nonrepeating, antigenic determinants.

Antibodies↗
PubMed1978

B lymphocyte subpopulations separated by velocity sedimentation. II. Characterization of tolerance susceptibility.

Neonatal and adult splenic B lymphocyte subpopulations, separated by velocity sedimentation, were tested in an in vitro splenic focus assay for their susceptibility to tolerance induction with hapten-protein conjugates. At least two tolerizable B cell subsets have been defined in the neonatal spleen; one comprising the slowly sedimenting, small lymphocytes and the other comprising the very rapidly sedimenting, large lymphocytes. In addition, a rapidly sedimenting large B cell subset in the adult spleen was found to be highly susceptible to tolerance induction. It was suggested that the inability to detect this susceptibility in unfractionated adult spleen was due to the low proportion of these very large lymphocytes in the total spleen cell population. The tolerizable B cell subsets presently defined probably represent the least mature B lymphocytes detectable in the splenic focus assay.

Aging↗
PubMed1978

Tolerance to azobenzenearsonate: preferential loss of the major normal cross-reactive idiotype.

A specific tolerant state was induced in A/J mice to the hapten p-aminobenzenearsonate (Ars) by the injection of deaggregated conjugates of Ars and human gemma-globulin (Ars-DHGG). The kinetics of tolerance to Ars-DHGG was found to be identical to that of B cell tolerance to human gamma-globulin alone. The ability to produce antibody (anti-Ars) bearing the major normal cross-reactive idiotype was found to be preferentially lost. In addition, recovery of the ability to produce anti-Ars bearing this cross-reactive idiotype was found to be delayed as compared to the total anti-Ars response upon spontaneous loss of tolerance.

Animals↗
PubMed1977

Antibody as immunological probe for studying refolding of bovine serum albumin. Refolding within each domain.

Antiserum to bovine serum albumin was fractionated into populations of antibody directed against party, an apparent pathway of refolding within each domain was obtained which is consistent with the proposed evolutionary pathway of the albumin molecule. The COOH-terminal one-third of each domain refolds faster than the NH2-terminal two-thirds of each respective domain. In addition, further evidence in given for a correlation between the rate of refolding and the degree of interdomain influence that might restrict refolding.

Amino Acids↗
PubMed1976

Antibody as an immunological probe for studying the refolding of bovine serum albumin. I. The catalysis of reoxidation of reduced bovine serum albumin by glutathione and a disulfide interchange enzyme.

We have used an immunochemical approach to study the refolding of bovine serum albumin. Using antibody as a probe for return of native structure, we have been able to demonstrate the regeneration of native structure at several sites on the surface of the molecule. Using this technique, we have shown that the rate of refolding of reduced bovine serum albumin catalyzed by either glutathione or rat liver disulfide interchange enzyme is greater than the rate of air reoxidation of albumin. The half-regeneration times for albumin, however, are substantially greater than those obtained with smaller proteins that have fewer disulfide bonds. We have also demonstrated that the reoxidized monomers isolated at the end of the refolding process are immunologically identical to native monomers. In addition, the tryptophan fluorescence emission maxima were the same as that of the native monomers.

Antibodies↗
PubMed1976

Antibody as an immunological probe for studying the refolding of bovine serum albumin. II. Evidence for the independent refolding of the domains of the molecule.

Antiserum to bovine serum albumin were used as a probe for native structure to study the process of refolding of denatured bovine serum albumin. Different antigenically active fragments that represent domains and subdomains of the molecule were isolated. Restricted populations of antibody to albumin were obtained by fractionating antisera to the native intact molecule on immunoadsorbents bearing these fragments. The restricted antibody populations were then used to probe the surface of the molecule during the refolding process. Some regions of the molecule refolded more rapidly than other regions. Isolated domains of albumin also refolded to native antigenic structure demonstrating that the entire polypeptide chain was not necessary for reformation of native structure. However, there does seem to be some interdomain influence on the rate of refolding of a particular domain within the intact protein.

Amino Acids↗