Identification of derepressed autoimmunocompetent B lymphoid cells in NZB mice.

Plaque assays for derepressed autoimmunocompetent B lymphoid cells with specificities for two murine erythrocyte surface autoantigens have been developed. Using purified anti-HB and anti-X anti-erythrocyte autoantibodies, fluid-phase complement fixation reactions were performed to determine the influence of pH and ionic strength on the efficiency of autoantibody-mediated cytolysis of murine erythrocytes. Anti-HB autoantibody exhibited optimal cytolysis of bromelin-treated erythrocytes at pH 7·0, ionic strength 0·15; haemolysis of intact erythrocytes by anti-X autoantibody was observed over a broad range with maximum sensitivity and specificity at pH 6·6, ionic strength 0·14.

Glomerular complement components in human glomerulonephritis.

154 of 255 individual human renal biopsies studied by immunofluorescence contained varying combinations of immunoglobulins (Ig), complement (C) components C1q, C3, C4, C5, C6, C8, C3 proactivator (C3PA), and/or properdin. 10 patients had linear deposits of Ig in glomeruli characteristic of antiglomerular basement membrane (GBM) antibodies; nine patients had C3 deposits (minimal in three) with generally lesser amounts of C1q, C4, C5, C6, and/or C8. 118 of the patients had granular deposits of Ig, suggesting immune complex glomerulonephritis; 114 of these had deposits of C3, usually accompanied by C1q, C4, C5, and/or C6.

The number of D and E regions in the fibrinogen molecule.

The regional structure of fibrinogen was considered in reference to the terminal plasmin-cleavage fragments, D and E. By two independent approaches, a yield of two D and two E fragments was determined and this established the presence of two D and two E regions in each fibrinogen molecule. Immunochemically, it was shown that the expression of native fibrinogen determinants by the D:E complex was fully reconstituted by an equimolar mixture of D and E fragments, while other recombinant ratios failed to yield optimal reconstitution.

Factor VIII coagulant activity and factor VIII-like antigen: independent molecular entities.

Factor VIII coagulant activity (VIII(C)) and the von Willebrand's disease antigen (Factor VIII-like antigen, vW-Ag) are biologically linked, and it has been suggested that they reside on the same molecule. However, insolubilized human isoantibody to VIII(C) and rabbit antiserum containing antibodies to VIII(C) and vW-Ag differentially bind and remove these entities from plasma, thus physically segregating one from the other. These findings indicate that Factor VIII coagulant activity resides on a molecule distinct from that expressing the von Willebrand's antigen.

Discriminating neoantigenic differences between fibrinogen and fibrin derivatives.

Discrimination between the physiological cleavage fragments of fibrinogen and fibrin offers an approach to differentiation between fibrinogenolytic processes and fibrinolysis after coagulation. By use of the cleavage-associated neoantigen of fibrinogen (fg-D(neo)) as a molecular marker, characteristic differences between the D regions of fibrinogen derivatives and fibrin derivatives can be demonstrated. The expression of fg-D(neo) by X, Y, D:E complex, and D-fragments of fibrinogen or fibrin is shown to be quantitative and unitary.

Immunobiology of the autoantibody response. I. Circulating analogues of erythrocyte autoantigens and heterogeneity of the autoimmune response of NZB mice.

Anti-erythrocyte autoantibodies of two distinct antigenic specificities can be recovered from immunoglobulin-coated NZB erythrocytes. These autoantibodies react with either exposed (X) or hidden (HB) antigenic determinants on murine red cells and both types can be neutralized by mouse plasma. Antibody neutralization by plasma is dependent on two distinct plasma activities which appear to be soluble analogues of the erythrocyte surface autoantigens X and HB.

Immunobiology of fibrinogen. Emergence of neoantigenic expressions during physiologic cleavage in vitro and in vivo.

Physiological degradation of fibrinogen by plasmin leads to a recognized series of intermediate and stable terminal cleavage fragments and is associated with complex modulation and progressive loss of native antigenic expressions. Early in association with progressive plasmin cleavage, a stable cleavage-associated neoantigen, present in the D-fragment region of the molecule, is exposed in vitro and can be recognized by competitive inhibition radioimmunoassay with specific antiserum. It is demonstrated that there is an approximate equimolar expression of the cleavage-associated neoantigen.

Molecular events responsible for modulation of neoantigenic expression: the cleavage-associated neoantigen of fibrinogen (blood coagulation-fibrinogen cleavage products-fibrinolysis-molecular conformation).

Molecular events responsible for modulation of neoantigenic expressions of a defined molecule have been explored in relation to three hypothetical molecular models (see below). Fibrinogen and its cleavage-associated neoantigen have been used as a prototype system. Physicochemical and enzymatic factors influencing neoantigenic expression were evaluated.