Serological Relationships between Nucleus, Cytoplasm, and Cytoplasmic Products and the Concept of Complementary Molecules

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Abstract
The concept that a similar template mechanism operates in the production of antibodies and in normal biological synthesis and growth leads to the theory that both antibodies and products of normal cell synthesis must be complementary to the substances acting as the sites of synthesis or templates for their formation. This theory is tested for liver cells and serum proteins. The rationale of the expts. is as follows: nuclear constituents serve as templates for synthesis of cytoplasmic elements which are thus complementary to nuclear constituents; cytoplasmic elements serve as templates for the synthesis of cytoplasmic products which are thus complementary to cytoplasmic constituents and homologous with nuclear constituents; serum proteins are products of hepatic cell cytoplasmic synthesis; in line with this reasoning, antibodies to nuclear elements should react with both nuclear elements and serum, but not with cytoplasm, antibodies to serum should react with serum and nuclear constituents, but not with cytoplasm, antibodies to cytoplasmic elements should react with cytoplasm but not with nucleus or serum. In the exptl. procedure separation of liver cell cytoplasm and nuclei is accomplished by the Dounce method; nucleohistones are extracted with 10% NaCl and dialyzed, these are the nuclear elements tested; antisera to rat liver cell nucleohistones, rat liver cell cytoplasm, and rat serum are prepared by injecting White Leghorn and New Hampshire fowl intramusc. or intraperitoneally with the appropriate antigens; antisera are collected 8 days after injections, and these antisera are tested by cross reaction with serial dilutions of all of the antigens involved. In a general way, the expected results are obtained. Antinuclear sera show high activity against nuclear constituents and under some conditions against serum; antiserum sera show high activity against serum and nuclear elements but not against cytoplasm. Anticytoplasmic sera show unexpectedly high titers against nuclear extracts, possibly due to fact that nuclear constituents normally pass into the cytoplasm in the living cell. Nuclear, cytoplasmic, and serum specificity, and further evidence for interrelations indicated above are derived from a series of absorption expts.