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Biomedical subjects

J M Davie

Publications and source records attributed to J M Davie.

At least 19 recordsLinked to original sources
PubMed1979

Prolongation of islet allograft survival following in vitro culture (24 degrees C) and a single injection of ALS.

Isolated rat islets remain morphologically and functionally intact during a 7-day period of in vitro culture at 24 degrees C. In vitro culture of islets at 24 degrees C for 7 days prior to transplantation, in conjunction with a single injection of antiserum to lymphocytes into the diabetic recipient, results in islet allograft survival of 100 days when the islets are transplanted across a major histocompatibility barrier.

Animals↗
PubMed1979

Immunoglobulin subclass-specific immunodeficiency in mice with an X-linked B-lymphocyte defect.

CBA/N mice express an X-linked deficiency in their antibody response to many bacterial carbohydrates; we have shown recently that these antigens normally elicit antibody responses predominantly of the IgM and IgG3 isotypes. Here we demonstrate that mice, with the CBA/N phenotype have perferential deficiencies of IgM and IgG3 immunoglobulin expression, both when measured in serum and in cells secreting these isotypes, and that this deficiency is only partially corrected by polyclonal activation of B cells. This suggests that CBA/N mice may lack a subpopulation of B cells that contain most of the IgG3 precursors.

Animals↗
PubMed1979

Immune response deficiency of BSVS mice. II. Generalized deficiency to thymus-dependent antigens.

BSVS mice gave abnormally low IgG responses to 5 thymus-dependent antigens as well as a weak delayed-type hypersensitivity (DTH) response to sheep red blood cells. In contrast to IgG, the IgM antibody responses of these mice were normal to three T-independent antigens as well as to all five T-dependent antigens. The low immune responsiveness of BSVS mice was also reflected in the low levels of IgG(2)a, IgG(2)b and IgG(3) in their normal serum. The low T-dependent immune responses may result from BSVS mice having been selectively bred for susceptibility to infection with St. Louis encephalitis virus and Salmonella. C57BL/6J mice, which are also highly susceptible to Salmonella, gave low immune responses similar to, but genetically distinct from, those of BSVS mice. The levels of Ig-positive and theta-positive cells were normal in BSVS and C57BL/6J mice.

Animals↗
PubMed1979

Prolongation of islet allograft survival.

Pretreatment of donor rats with irradiation and silica followed by in vitro culture of the islets for 1 to 2 days prolonged survival of allografts across a minor histocompatibility barrier if "hand-picked," clean islets were used for transplantation. Pretreatment of donor rats with irradiation and silica in conjunction with a single injection of antilymphocyte serum (ALS) into the recipient produced a prolongation of survival of hand-picked islets transplanted across a major histocompatibility barrier.

Animals↗
PubMed1979

Analysis of the diversity of murine antibodies to dextran B1355: N-terminal amino acid sequences of heavy chains from serum antibody.

The N-terminal amino acid sequences of two gamma and two mu chains from normally induced serum antibodies to dextran in BALB/c mice are presented. These heavy chains are derived from antibodies with three distinguishable idiotypes. These variable region (VH) sequences are all identical as far as they have been analyzed (27 to 53 residues). The light chains from these antibodies are all of the lambda type and are identical by isoelectric focusing analysis. Accordingly, the diversity of dextran antibodies appears to reside primarily in the heavy chains. The implications of these observations for antibody diversity are discussed.

Amino Acid Sequence↗
PubMed1978

Analysis of the diversity of murine antibodies to dextran B1355. III. Idiotypic and spectrotypic correlations.

Examination of 19 S and 7 S anti-alpha(1 leads to 3) dextran (Dex) antibodies by serological assays and isoelectric focusing (IEF) has revealed substantial variation of idiotypic and spectrotypic expression between individuals of the same genotype. 7 S antibodies appeared to be more heterogeneous than 19 S by both methods. A strong, but complex, association was found between the IEF patterns of 19 S and 7 S anti-Dex antibodies and their expression of the idiotypic determinant(s) common to both the M104 and J558 dextran-binding myeloma proteins. However, no such relationship was found between the IEF pattern and the expression of idiotypic determinant(s) unique to the M104 myeloma protein. Rather, indistinguishable spectrotypes from different individuals have widely differing levels of expression of the determinant. In addition, this determinant(s) may be present on different spectrotypes of the same isotype. Both the M104 and J558-specific idiotypes were found on antibodies of the IgG3 subclass as well as in pools containing predominantly the IgG2a subclass. These data confirm and extend the picture of substantial structural variation among the antibodies comprising a response of restricted heterogeneity.

Animals↗
PubMed1978

Regulation of anti-hapten antibody secretion by carrier-specific suppressor T cells.

Carrier-primed T lymphocytes can suppress high avidity IgG anti-hapten antibody secretion within 90 min. in vitro if the suppressor and target cells are primed with the same carrier determinants. Suppression seems to be directed to the antibody secreting cell since the effect is rapid and does not depend on macrophages or T cells in the target cell population. Suppression can be blocked by inclusion of soluble carrier in the cell mixture or by treatment of the target cells with anti-carrier antibody or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be altered by preincubation of the target population with a hapten-heterologous carrier before addition of suppressor cells specific for the heterologous carrier. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody secreting cells which serves as a target for suppressor cells or molecules.

Animals↗
PubMed1978

Subclass restriction of murine anti-carbohydrate antibodies.

Examination of the subclass distribution of murine antibodies directed against groups A and C streptococcal carbohydrate, alpha-(1 leads to 3) dextran and phosphocholine yields the surprising observation that these carbohydrate antigens stimulate IgG responses largely restricted to the rare IgG3 subclass. This subclass restriction is particularly impressive in light of the low circulating levels of IgG3 in nonimmune mouse serum and the failure of a variety of other antigens including proteins and aromatic haptens to stimulate IgG3 antibody production. Attempts to alter the subclass restriction of antibodies with carbohydrate specificity by immunization with carbohydrate-coupled protein have been unsuccessful and indicate that immunoregulation of subclass expression probably occurs at the level of the antibody forming (B) cell. It is therefore conceivable that VH regions of murine immunoglobulins may be restricted to particular IgG subclasses. A similar type of subclass restriction has been reported in human and rat anti-carbohydrate antibodies. This recruitment of a minor immunoglobulin isotype by carbohydrate antigens in several species further supports the concept of immunoregulation at the level of subclass, and suggests that these and other mammals may share a structurally similar isotype with perhaps a common evolutionary origin.

Animals↗
PubMed1978

Light chain diversity of murine anti-streptococcal antibodies: IgCH-linked effects on L chain expression.

L chains derived from anti-group A streptococcal carbohydrate antibodies raised in A/J, BALB/cJ, C57BL/6J, CB-20, BAB-14, and CAL-20 mice were examined by isoelectric focusing. Multiple strain-associated differences in the degree and frequency of expression of particular L chain spectrotypes were observed. Analysis of L chain-focusing patterns in allotype-congenic mice revealed that IgCH-linked genes can have profound effects on the L chain phenotypes expressed by strains with identical L chain genotypes. Lastly, the overall spectrotypic diversity of L chains from anti-GAC antibodies appears to be less extensive than the diversity of the antibodies from which these L chains derive, documented by similar techniques. These results are interpreted in light of the significance of combinatorial diversity in generating antibody heterogeneity.

Animals↗
PubMed1977

Antigen mediation of a late-acting suppressor T-cell activity.

Carrier-specific suppressor T cells can suppress antibody secretion by high avidity IgG plaque-forming cells (PFC) within 90 min in vitro. This process can be blocked by the inclusion of soluble carrier in the cell mixture or by the exposure of target cells to anti-carrier antibodies or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be overcome by preincubation of the target population with a hapten-heterologous carrier before addition of heterologous carrier ATC. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody-secreting cells which serves as a target for suppressor cells or molecules.

Animals↗
PubMed1977

Isoelectric focus analysis of rat anti-phosphocholine antibodies.

Anti-phosphocholine (PC) antibodies in sera from four strains of rats were examined before and afterimmunization with either Streptococcus pneumoniae R36A, which contains PC as a cell wall component, or with PC-coupled keyhole limpet hemocyanin (PC-KLH). PC-specific protein was purified from pooled immune sera and shown by a combination of isoelectric focus (IEF) in acrylamide and crossed immunoelectrophoresis, as well as by molecular weight determination in NaDodSO4-acrylamide, to be immunoglobulin. An additional, small molecular weight, nonimmunoglobulin protein (pI = 7.1-7.3) was present in sera from normal and germ-free rats which had the ability to bind the C-carbohydrate of S. pneumoniae R36A, but without specificity for PC. The IEF profile of normal and immune sera showed marked sharing of bands of anti-PC antibody between individual rats as well as between strains. In addition, other anti-PC antibodies which focused between pH 8.5 and 9.5 were less regularly shared. The uniformity of IEF profile of the bulk of anti-PC antibodies in rats is most consistent with their being the products of germ line genes.

Animals↗
PubMed1977

Role of T lymphocytes in the humoral immune response III. Lack of influence of antigen charge on the isotype and charge of antibody.

The influence of antigen charge on the anti-hapten antibody response and antigen-stimulated blastogenic response in vitro was measured in guinea pigs. The animals were immunized with dinitrophenylated bovine albumin (DNP-BSA; pl 4.9), methylated DNP-BSA (DNP-MBSA; pl greater than 10), and DNP-lysozyme (pl greater than 10). While the lymph node lymphocytes clearly distinguished between DNP-BSa and DNP-MBSA in terms of the magnitude of the antigen-stimulated 3H-thymidine incorporation, no differences were seen with respect to the characteristics of the antibody response. Thus, IgG1-to-IgG2 ratios, DEAE cellulose fractions and isoelectric focus profiles of anti-DNP sera from animals immunized with DNP-BSA, DNP-MBSA and DNP-lysozymes were indistinguishable.

Animals↗
PubMed1977

Functional, structural, and antigenic similarities of guinea pig anti-phosphorylcholine antibodies.

The humoral immune response to PC was measured in guinea pigs. PC-vaccine stimulated IgM and IgG2, but little IgG1, anti-PC -antibodies. No memory was induced and immunization in CFA produced tolerance. PC-KLH, on the other hand, stimulated IgM, IgG2, and IgG1 anti-PC antibodies with carrier-specific memory. Hapten inhibition of plaque formation showed uniform binding patterns with minor, but significant, differences between antiPC-vaccine and anti-PC-KLH antibodies. The antibodies were characterized by IEF and idiotypic analyses. Early after immunization with PC-vaccine, guinea pigs had restricted IEF patterns which in inbred, but not outbred animals were indistinguishable between individuals. These patterns remained restricted but more individualized with time after immunization. Anti-PC-KLH antibodies showed more heterogeneity and individuality. However, these structurally heterogeneous antibodies reacted equivalently with rabbit anti-idiotype antisera and therefore must share common structural features, regardless of isotype or the genetic background of the guinea pig.

Animals↗
PubMed1977

Late acting T cell depression of high avidity IgG antibody secretion in the secondary response.

Activated T lymphocytes (ATC) suppressed the expression of high avidity plaque-forming cells (PFC) in the secondary immune response when given in vivo 1 day before assay or when mixed in vitro with hyperimmune cells for 90 min before assay. This late acting suppression is a cell dose-dependent, carrier-spedific, T cell-mediated phenomenon. The target of this activity if probably the antibody-secreting cell.

Animals↗
PubMed1977

Complete sharing of light chain spectrotypes by murine IgM and IgG anti-streptococcal antibodies.

In order to examine the diversity of antibody light chains, we have developed an analytic isoelectric focusing procedure which permits the routine analysis of L chains from antibodies raised in individual mice. We have used this technique to demonstrate that the light chains of IgM and IgG anti-group A streptococcal antibodies raised in SWR mice are probably shared. Interestingly, numerous light chain spectrotypes are shared between individual mice whose 7S antibody focusing patterns differ.

Animals↗
PubMed1977

Analysis of the diversity of murine antibodies to dextran B1355. II. Demonstration of multiple idiotypes with variable expression in several strains.

We have developed radioimmunoassays that detect idiotypic (variable region) differences among the alpha(1 leads to 3) dextran-binding meyloma proteins U102, J558, and M104 as well as an assay that detects variable region determinants common to all three proteins. Using these assays, we have examined 7S and 19S anti-alpha(1 leads to 3) dextran antibodies induced in five murine strains of the a1 IgCH linkage group and the recombinant strain BAB/14. All idiotypes were expressed in both 19S and 7S antibodies from all strains, but with considerable strain-specific variability in penetrance. In two strains, one additional type of antibody, which lacked all four idiotypic determinants, generally constituted the bulk of total anti-alpha(1 leads to 3) dextran antibodies.

Animals↗
PubMed1977

Characterization of molecular heterogeneity and multispecificity in homologous idiotypic antisera.

The molecular heterogeneity of homologous anti-idiotypic reagents was characterized by a novel isoelectric focusing procedure. Idiotypic antisera directed against the PC-binding plasmacytoma protein T15 were raised in CE and and A/J mice. These antisera were shown to be highly specific by hemagglutination with myeloma protein-derivatized sheep erythrocytes and by radioimmunoassay. Competition experiments performed with affinity-labeled T15 revealed that about 40% of the pooled CE antibody activity was directed against binding site-associated determinants. Further analysis of anti-idiotypic sera from individual animals with the use of isoelectric focusing disclosed heterogeneous populations of antibody molecules distinguishable by isoelectric point and by subspecificity. Each animal expressed a unique spectrotypic profile. In addition, clones reactive with binding site and non-binding-site determinants as well as some clones with specificity for other PC-binding mouse myeloma proteins were detected. These results emphasize the importance of careful selection and thorough absorption of idiotypic antisera.

Animals↗