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M C Sneller

Publications and source records attributed to M C Sneller.

62 records · Page 4Linked to original sources
PubMed1988

Molecular analysis of membrane gamma 2b heavy chain expression.

In order to study T cell regulation of B cell isotype differentiation we have developed a model system consisting of clonal populations of T and B cells. Using this system we have shown that the murine B cell lymphoma, 70Z/3, can be induced to express membrane IgG2b by exposure to a T cell hybridoma derived from the Peyer's patch (termed HAJ-3). The membrane bound IgG2b (mIgG2b) expression is associated with induction of gamma 2b-mRNA, but switch region rearrangement and C mu deletion does not occur. While LPS-stimulated 70Z/3 B cells also express considerable amounts of gamma 2b-mRNA they do not express detectable mIgG2b, indicating that T cell influence is necessary for the production of translatable gamma 2b-specific mRNA. Both the LPS and T cell induced gamma 2b mRNA transcripts lack VH sequences, implying that the surface IgG2b detected lacks a variable region. These findings lend support to a two step model of B cell isotype switching and provide evidence that T cells can regulate early events involved in B cell isotype differentiation.

Animals↗
PubMed1987

DNA methylation alters chromatin structure and regulates Thy-1 expression in EL-4 T cells.

Thy-1 exhibits marked differences in expression in various tissues in many species; therefore, it is of interest to define possible mechanisms that may regulate Thy-1 expression. We produced Thy-1 negative variants of the murine T cell lymphoma EL-4 by mutagenesis with ethylmethanesulfonate (EMS), negative selection with anti-Thy-1 monoclonal antibodies (mAb) plus complement, and fluorescence-activated cell sorting (FACS). Thy-1 surface negative (Thy-1-) mutants produced in this manner were shown to produce no detectable Thy-1 mRNA, but contained an intact Thy-1 gene as determined by Southern blotting. 5' CG sequences, which had been demethylated in the parent EL-4 clone, were completely methylated in the EMS-induced Thy-1-variant. In addition, a DNase I hypersensitive site that mapped to the 5' end of the Thy-1 gene in EL-4 was absent in the Thy-1- variant. Treatment of this Thy-1- clone with 5-azadeoxycytidine (5-dAZA) resulted in re-expression of surface Thy-1, demethylation of the 5' CG sequences, and regeneration of the DNase I hypersensitive site. These studies indicate that methylation of certain critical DNA sequences in the 5' region of the Thy-1 gene can alter local chromatin structure and regulate expression of this gene.

5-Methylcytosine↗
PubMed1986

T cell-induced expression of membrane IgG by 70Z/3 B cells.

To study T cell regulation of B cell isotype differentiation, we determined the capacity of clonal T cell populations (hybridomas derived by fusing BW5147 with Con A-activated Peyer's patch (PP) and spleen T cells) to induce "downstream" isotype expression by the pre-B cell lymphoma 70Z/3. In initial studies, we found that 70Z/3 B cells cultured in the presence of LPS (1 microgram/ml) expressed membrane IgM (mIgM) but not membrane IgG (mIgG). In contrast, 70Z/3 B cells cultured with HAJ-3 T cells, a PP-derived T cell hybridoma (as well as other similarly derived PP and spleen hybridomas), or with HAJ-3 T cells plus LPS do express mIgG. Such expression occurred in spite of mitomycin C-induced blockage of cell proliferation, and is observed in 70Z/3 B cell subclones cultured with HAJ-3 T cells. For these reasons, it is not due to selective expansion of a small pre-switched mIgG-bearing 70Z/3 B cell subpopulation. In other studies it was shown that 70Z/3 B cells expressing mIgG after induction by HAJ-3 T cells continue to express mIgM and do not secrete IgG. Finally, exposure of 70Z/3 B cells to the macrophage factor IL 1 and the T cell factors IL 2, BSF-pl, and BCGF-II present in EL-4 cell supernatants did not result in mIgG expression. On the basis of these studies, we conclude that a clonal B cell population expressing mIgM can be induced by T cells to co-express mIgG. Because the B cells do not express mIgG unless exposed to T cells, this represents a T cell-induced isotype switch.

Animals↗
PubMedDate not supplied

Orbital involvement in Wegener granulomatosis: MR findings in 12 patients.

PURPOSE: Our goal was to characterize the MR features of orbital Wegener granulomatosis (WG). METHOD: Twelve patients with pathologically proven WG were studied with MRI. Enhanced and unenhanced T1-weighted sequences with conventional and fat-suppressed techniques were used. T2-weighted images were also obtained. Signal intensity measurements were made in each orbital lesion on the T2-weighted images and compared with that of normal fat. The degree of enhancement was also evaluated by measuring the change in signal intensity of each lesion between the unenhanced and enhanced studies. RESULTS: Seventeen orbital lesions were identified in the 12 patients. Fifteen of the lesions examined by T2-weighted sequences demonstrated a marked decrease in signal intensity. The unenhanced, non-fat-suppressed T1-weighted sequences provided the best contrast between lesion and normal structures. All of the WG lesions enhanced, but the degree of enhancement varied. The enhancement characteristics were best appreciated on the fat-suppressed T1-weighted technique. CONCLUSION: MRI is an excellent imaging modality to evaluate orbital involvement in WG. A marked decrease in the T2 signal is a characteristic feature of this entity. The unenhanced, non-fat-suppressed T1-weighted sequence is the preferred method for lesion detection and for definition of the pattern of anatomic involvement when utilizing MRI.

Adult↗