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The previous observations of cross idiotypic specificity of IgM cold agglutinins were further investigated in quantitative precipitin assays and attempts were made to relate shared idiotypic specificity to combining specificity for I, i and Pr antigens of red cells. Shared idiotypic determinants were observed among antJ-I and anti-i antibodies which are now known to have combining specificity for determinants present on precursors of the ABH and Lewis blood group substances. There was evidence that one cold agglutinin. Ma, which had previously been shown to have an unusual kind of I specificity was deficient in the idiotypic determinants associated with the other anti-I proteins. Anti-Pr cold agglutinins, which have specificities unrelated to I-i antigens, were found to have distinct cross idiotypic determinants which were not detected on anti-I and anti-i antibodies. IgA and IgM antibodies with Pr specificity isolated from different individuals were found to share idiotypic determinants. Cross specificity antigens were detected at low concentrations in preparations of normal IgG and IgM, but not in any isolated monoclonal macroglobulins lacking cold agglutinin activity. [ABSTRACT FROM AUTHOR]

Highly purified preparations of dendritic cells were obtained from human peripheral blood. Loosely adherent cells were selected and subsequently depleted of phagocytic cells and Fc receptor positive cells to yield the dendritic cell fraction. These isolates contained greater than 90% Ia positive cells, with many of the cells showing the morphological characteristics of the murine dendritic cell. These preparations were compared to other mononuclear cell fractions as stimulating cells in autologous and allogeneic mixed leucocyte reactions. The dendritic cell preparations provided the most potent stimulus for autologous T cell proliferation, with 10 × more 3H-thymidine incorporated by T lymphocytes incubated with autologous dendritic cells than with any other non-T cell preparation. Dendritic cells were also the most stimulatory cell in the allogeneic mixed leucocyte reaction, although the non-adherent subpopulation produced some stimulation of allogeneic T cells. In separate experiments, it was determined that B cells could be activated by pokeweed mitogen to vigorously stimulate autologous T cells. Visual observation of cluster formation in cultures containing dendritic cells and autologous T cells suggests that the capacity for intimate cell contact may be an important property of the dendritic cell in vivo. [ABSTRACT FROM AUTHOR]

Antibodies to surface determinants of human lymphocytes, recognized both by cytotoxicity and fluorescent antibody analysis, were shown to be specifically enriched over the serum levels in cryoprecipitates from patients with systemic lupus erythematosus (SLE). The antilymphocyte antibody was shown to be cold reactive and was exclusively IgM. It was distinct from IgM anti-IgM, which was also variably concentrated in the cryoprecipitates. The question whether the antilymphocyte antibodies appear in the cryoprecipitates as complexes because of interaction with surface membrane antigens, or simply because of cold reactive properties, remains to be determined. The possible clinical relevance of the cryoprecipitation of these antibodies in systemic lupus erythematosus is discussed. [ABSTRACT FROM AUTHOR]

Unmeasurable total haemolytic complement (C) was observed in serum of a patient with untreated chronic lymphocytic leukaemia and recurrent non-hereditary angioedema. Analysis of C components immunochemically demonstrated a marked reduction of Clq and Cls inhibitor, undetectabie Clr, C-ls and an elevated B. Haemolytic Cl, C4 and C2 were less than 5% of normal, functional Cls inhibitor was absent. Cryoglobulin and Clq precipititis were present in the serum. Of special interest was the presence of high levels of cold-reactive antilymphocyte antibody, determined by both C-dependent cytotoxicity and indirect immunofluorescence. The antibody exhibited specificities for both autologous lymphocytes and lymphocytes from normal donors; cytotoxic activity for autologous leukaemia cells was removed by absorption with normal isologous tonsil lymphocytes. Specific enrichment of this antibody relative to the serum level was demonstrated in the cryoglobulin and its isolated 19S fractions. Free lymphocyte surface antigen was also demonstrated by gel diffusion using specific rabbit antilymphocyte antiserum. These data strongly suggest the presence of pathogenetically significant circulating complexes of lymphocyte surface antigen and specific antibody in certain patients with CLL. [ABSTRACT FROM AUTHOR]

Four cases of hairy cell leukemia were studied by immunofluoroscence. All hairy cells bore surface immunoglobulin. In two cases, only IgD was detected on the cell surface, whereas both IgM and IgD were present in the other two cases. After adsorbed IgG was removed by overnight culture, only one class of light chains was detected. In addition, most of the hairy cells were capable of ingesting latex particles. These findings suggest that hairy cell leukemia is caused by a monoclonal proliferation of a type of Ig-bearing B cell with phagocytic potential. [ABSTRACT FROM AUTHOR]

Murine monoclonal antibodies (MoAb) were prepared by immunizing mice with human monoclonal rheumatoid factors from patient with mixed cryoglobulinaemia. Indirect solid phase radioimmunoassay and haemagglutination inhibition were used to screen the MoAb, Reacuity patterns of MoAb were determined using (a) polyclonal and monoclonal lgM proteins. (b) monoclonal IgM proteins Iron patients with neuropathy (c) monoclonal and Polyclonal IgM antigammaglobulins and (d) various isolated VkIII -positive immunoglobulins. Several patterns were obtained: MoAb reacting with private idiotype's determinants. with VkIlIb-related determinants. and with cross reactive idiotypes (CRI). Two .MoAb of the second type reacted with VkllIb-positive immunoglobulins and light chains regardless of their antigenic activity. Another MoAb reacted with VKIII light chains only when in association with μ heavy chains. MoAb at the third type detained distinct CR1 systems. One of these was restricted to antigammaglobulins and another also involved neuropathy associated monoclonal IgM proteins. All MoAb clearly reacted with a minor population or normal polyclonal IgM. except for the MoAb detecting private idiotype determinants. Studies using inhibition of binding by enzyme-linked immunosorbents assay showed that polyclonal IgM antigammaglobulins `nay carry a CRI determinant detected by one ot the MoAb. This CRI system. defined by the MoAb Gb 86.3, was similar to but not identical with the previously described CRI which is widely prevalent among IgM antigammagiobulins of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The T-cell differentiation antigen T4/Leu3 has been described as a non-polymorphic molecule important in T-cell recognition of class II major histocompatibility complex antigens. We report the polymorphism of this molecule in black individuals as manifest by a heterogeneity of staining with OKT4 monoclonal antibody. No such heterogeneity was observed when staining with other monoclonal antibodies that bind to different epitopes of the same molecule. No heterogeneity of staining with any of the monoclonal antibodies was observed in whites. Three patterns of OKT4 staining emerged: intact, deficient, and intermediate. This heterogeneity is likely to be due to an intrinsic heterogeneity in T4 epitope expression and not secondary to an interfering plasma factor as shown by the preservation of the T4 epitope pattern after a 3-day culture; in the presence or absence of mitogen. Family studies strongly suggest that this heterogeneity in T4 epitope expression is inherited in an autosomal codominant fashion. [ABSTRACT FROM AUTHOR]

Eleven selected patients with chronic lymphocytic leukaemia were evaluated for lymphocyte binding of aggregated IgG and surface Ig staining in order to classify them into B and T cell types. Ten of the eleven patients bound aggregates and stained for surface Ig. In the individual ten patients the number of cells binding aggregates was high (88-100% mean 96%) whereas the number staining for surface Ig was more variable (8-100%, mean 62%). Parallel and double labelling experiments with aggregates and sheep red blood cell rosettes, a human T cell marker, provided evidence that aggregates were binding to B cells only, even when surface Ig was not detectable. Aggregates did not bind to human thymocytes. Evidence was presented that lymphocytes from some cases of CLL have low but not absent amounts of surface Ig that may be only partially detected by fluorescence techniques. Aggregate binding appears to be a more sensitive method for the detection of B lymphocytes than surface Ig staining. In one of the eleven patients the leukaemic cells were negative in the aggregate binding test. Separate studies on this case also indicated an absence of surface Ig staining and a high percentage of cells forming sheep red blood cell rosettes. It would appear that this case represented a T cell leukaemia. [ABSTRACT FROM AUTHOR]

Gamma globulin complexes were demonstrable in certain joint fluids from patients with rheumatoid arthritis by analytic and density gradient centrifugation. They form a continuum of high molecular weight components ranging from 7S to 30S and were dissociable primarily to 7S γG globulin. The larger complexes were also detectable by precipitation reactions with C1q and with γM rheumatoid factor. This permitted the isolation and partial characterization of the complexes. Non-immunoglobulin constituents were not detectable. Evidence was obtained that 7S γG globulin rheumatoid factors represented an important constituent of the complexes. A relationship was encountered between the amount of γ globulin complex present in the joint fluids and diminution in total haemolytic complement activity. All fluids with abundant γ globulin complexes contained markedly lowered complement levels. A decrease in levels of C1q and β1A was found to correlate with the amount of γG globulin complexes. Although patients who had diminished complement levels in their joint fluid have serum γM rheumatoid factor, its titre does not correlate well with the extent of complement depression. Joint fluids with abundant γ globulin complexes manifested an anticomplementary effect. This activity was most apparent at 37°C when fresh rheumatoid serum was used as a source of complement. Evidence indicating the participation of γM rheumatoid factor in this anticomplementary effect was obtained. All fluids with significant anticomplementary activity formed precipitin bands with C1q on agarose plates. γM rheumatoid factor was not necessary for this reaction. [ABSTRACT FROM AUTHOR]

The article presents information on a study which used the labelled DNA in the ammonium sulphate precipitation technique to demonstrate DNA antibodies in the sera of patients with systemic lupus erythematosus. Whereas only nineteen of thirty-seven sera studied had demonstrable precipitins, thirty-three had significant binding ability for native DNA with this more sensitive assay. The ammonium sulphate precipitation technique detects a broad spectrum of antibodies whereas precipitin tests, complement fixation, and haemagglutination measure select populations of antibody.

A gel diffusion method for demonstrating precipitin reactions of Clq with aggregated γ-globulin and immune complexes is described. Optimal precipitin lines were found to occur with 0.6 per cent agarose in 0.01 M EDTA at pH 7.2 and ionic strength 0.1. Reduction and alkylation of γ-globulin aggregates destroyed the precipitability with Clq. Precipitation occurred only with aggregates greater than 19S and with soluble immune complexes formed in two to twenty times antigen excess. γ-Globulin complexes were detected by this procedure in hypocomplementaemic sera from patients with systemic lupus erythematosus and hypocomplementaemic joint fluids from patients with rheumatoid arthritis. The relevance of this in vitro system to in viva complement consumption in various disease states is discussed. [ABSTRACT FROM AUTHOR]