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R M Perlmutter

Publications and source records attributed to R M Perlmutter.

118 records · Page 7Linked to original sources
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↗
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.

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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.

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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.

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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

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.

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PubMedDate not supplied

Molecular genetics of anti-carbohydrate antibodies.

Antibodies directed against carbohydrate determinants provide useful model systems for understanding the structure and organisation of antibody genes and the generation of antibody diversity. We have used three such systems, PC, DEX and GAC, and have studied the heavy chains and VH gene segments of each. In two of these systems, PC and GAC, much of the diversity in heavy-chain protein sequences results from somatic mutation events superimposed on expression of a single VH gene. In the DEX system, it appears that germ-line sequence diversity may be an important contributor to the variability in heavy-chain sequence. Detailed structural analyses of this type will ultimately provide a complete picture of the mechanisms which underlie effective humoral immunity.

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PubMedDate not supplied

A novel 6:10 chromosomal translocation in the murine plasmacytoma NS-1.

Specific chromosomal abnormalities are regularly associated with many murine and human malignancies. In particular, the majority of murine plasmacytomas and human Burkitt's lymphomas contain a characteristic translocation which results in the juxtaposition of a cellular oncogene, c-myc, with the immunoglobulin heavy-chain gene locus, and this rearranged c-myc directs the synthesis of qualitatively and quantitatively abnormal transcripts which may have an aetiological role in the development of the transformed state in lymphoid malignancies. Similarly, rearrangement and abnormal expression of c-myb (ref. 10) and c-mos (ref. 11) has been reported in other murine lymphoid tumours. Here we describe a novel 6:10 chromosomal translocation in the murine plasmacytoma cell line NS-1 which juxtaposes the immunoglobulin Ck gene with a single-copy sequence of unknown function. The NS-1 plasmacytoma is a frequently used fusion partner in hybridoma production and is known to contain a rearranged c-myc gene and a genetic element which transforms normal mouse fibroblasts in DNA-mediated transfection assays. We conclude that individual B-cell tumours may contain multiple chromosomal translocations perhaps relevant to oncogenesis.

Animals↗
PubMedDate not supplied

CD22 regulates thymus-independent responses and the lifespan of B cells.

The B-lymphocyte-restricted glycoprotein CD22 is expressed on mature IgM+IgD+ B cells, and is capable of binding to ligands on T and B cells. CD22 can interact with both the B-cell antigen receptor (BCR) complex and signalling molecules, including the protein tyrosine phosphatase SHP1 (PTP1C, SHP), a putative negative regulator of BCR signalling. Thus CD22 may facilitate interactions with lymphocytes and regulate the threshold of BCR signalling. To define the in vivo function of CD22, we generated CD22-deficient mice. Here we show that CD22 is required for normal antibody responses to thymus-independent antigens and regulates the lifespan of mature B cells.

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