Thomas B. Tomasi

The gamma(1)A present in saliva and colostrum exists largely in the form of higher polymers, the major component of which has a sedimentation coefficient of 11S. The 11S gamma(1)A in these fluids differs from the polymers found in normal and myeloma sera both immunologically and by the fact that their sedimentation coefficients are unaffected by disulfide bond reduction in the absence of urea. However, like other gamma-globulins the 11S gamma(1)A molecules consist of multiple polypeptide chains linked by disulfide bonds. Local synthesis of gamma(1)A in the salivary gland has been shown by fluorescent and autoradiographic studies, although the fraction of the total salivary gamma(1)A which is derived from local production is uncertain. No evidence of transport of intravenously administered I(131)-labeled 7S gamma(1)A from serum to saliva was obtained. Immunological specificity has been demonstrated in the salivary and colostral gamma(1)A. Whether that portion of the gamma(1)A which is immunologically specific is a piece incorporated during the local synthesis of gamma(1)A in the gland or is added by the epithelial cell in the process of transport remains to be determined. Antibody activity (isohemagglutinins) have been demonstrated in saliva and colostrum and have been shown to be of the gamma(1)A-type. In both of these fluids activity is associated primarily with gamma(1)A-polymers of 11S and 18S sizes. There appears to be an immunological system which is characteristic of certain external secretions. Its properties including the local production of a distinctive type of antibody separate it from the "systemic" system responsible for the production of circulating antibody. This system may play a significant role in the body's defense mechanisms against allergens and microorganisms.

Summary A tissue antigen reactive with sera from SLE patients has been partially characterized. The antigen is a soluble cytoplasmic component which is present in a variety of human tissues and is distinct from known nuclear antigens. It is an acidic macromolecule which has the electrophoretic mobility of an α1 globulin and is resistant to most proteolytic enzymes including trypsin, pepsin and chymotrypsin. Antigenicity is destroyed by 0.02 M periodate and by 0.001 M parahydroxy mercuribenzoate. Antibodies to this antigen have been found in 40% of unselected LE sera and were absent from a large number of sera from normal persons and from the sera of patients with other connective tissue disorders.

Epigenetic mechanisms are involved in regulating chromatin structure and gene expression through repression. In this study, we show that histone deacetylase inhibitors (DAIs) that alter the acetylation of histones in chromatin enhance the expression of several genes on tumor cells including: MHC class I, II, and the costimulatory molecule CD40. Enhanced transcription results in a significant increase in protein expression on the tumor cell surface, and expression can be elicited on some tumors that are unresponsive to IFN-gamma. The magnitude of induction of these genes cannot be explained by the effect of DAIs on the cell cycle or enhanced apoptosis. Induction of class II genes by DAIs was accompanied by activation of a repressed class II transactivator gene in a plasma cell tumor but, in several other tumor cell lines, class II was induced in the apparent absence of class II transactivator transcripts. These findings also suggest that the abnormalities observed in some tumors in the expression of genes critical to tumor immunity may result from epigenetic alterations in chromatin and gene regulation in addition to well-established mutational mechanisms.