Biomedical subjects

H H Birdsall

Publications and source records attributed to H H Birdsall.

23 records · Page 2Linked to original sources

PubMed1984

Regulation of antibody release by naturally occurring anti-immunoglobulins in cultures of pokeweed mitogen-stimulated human peripheral blood lymphocytes.

Immunoregulatory influences of human anti-immunoglobulins (anti-Ig) were studied in cultures of peripheral blood lymphocytes (PBL) from 11 normal donors. Pokeweed mitogen (PWM)-stimulated PBL released anti-Ig specific for Fab or Fc fragments of IgG, often within the first 24 to 72 hr in vitro. PBL that released more than 1 ng/ml IgM anti-Fab during the first 72 hr in vitro ultimately produced significantly less antibody (Ab) by the 12th day than PBL that released no detectable IgM anti-Fab during the first 3 days in culture. Adding affinity-purified human anti-Fab to PWM-stimulated PBL also suppressed the later Ab release by these cells. Suppression was polyclonal, affecting IgM anti-Fc, IgM anti-Fab, and IgM anti-tetanus toxoid Ab, and was directly dependent on the quantity of anti-Fab added. Anti-Fab Ab, isolated from single donor sera, were more suppressive, nanogram for nanogram, than were equal quantities of IgG anti-Fab obtained from Cohn Fraction II, when added to autologous donor PBL in vitro. Affinity-purified IgM anti-Fc, from pooled rheumatoid arthritis patient sera, also suppressed Ab release by PWM-stimulated PBL in a dose-dependent manner. These observations suggest that anti-Ig may exert a significant immunoregulatory role in man that can override to some extent the T cell-dependent stimulus for polyclonal B cell activation provided by PWM.

Antibodies, Anti-Idiotypic↗

PubMed1983

Anti-Fab' antibodies in rheumatoid arthritis. Measurement of the relative quantities incorporated in soluble immune complexes in sera and supernatants from cultured peripheral blood lymphocytes.

High levels of anti-immunoglobulins that react with Fab' fragments of IgG have been observed in sera of patients with rheumatoid arthritis (RA). To determine how much of these anti-Fab' antibodies are incorporated within immune complexes (IC), we added 125I-Fab' to sera and then measured the amount of labeled Fab' that could be precipitated by adding polyethylene glycol (PEG). Sera were either maintained at neutral pH during this procedure or acidified (pH 3) to dissociate IC. Acidification permitted the 125I-Fab' an equal chance to compete with other endogenous antigens for anti-Fab' antibodies, once excess hydrogen ion was removed. Quantities of anti-Fab' in sera of 20 seropositive RA patients were greater than in sera of 43 age- and sex-matched healthy controls, as measured by this assay and by a solid phase radioimmunoassay. However, significantly less anti-Fab' antibody was incorporated in ICs in the RA patients' sera. Supernatants from cultured peripheral blood lymphocytes of RA patients also contained relatively more "free" and less "hidden" anti-Fab' than culture supernatants from controls. Thus there appear to be qualitative as well as quantitative differences in the anti-Fab' antibodies synthesized by RA patients. This may reflect different proportions of IgM and IgG anti-Fab' in their sera, differences in the average avidity of these antibodies, or differences in the reciprocal relationships within the idiotypic network that result in release of antibodies by certain antibody-producing cells, but not by clones that produce complementary idiotypes.

Adult↗

PubMed1983

Characterization of anti-Fab' antibodies in human sera: identification of soluble immune complexes that contain hidden anti-KLH and blocking anti-immunoglobulins following immunization with keyhole limpet haemocyanin.

After immunization with keyhole limpet haemocyanin (KLH), increased concentrations of anti-KLH and anti-Fab' antibodies (Abs) were demonstrated in sera from 18 of 20 volunteers. In many cases, post-immunization sera contained soluble immune complexes that incorporated both anti-Fab' and 'hidden' or 'blocked' anti-KLH antibodies. The complexes containing hidden anti-KLH and blocking anti-Fab' Abs were not found in pre-immunization sera. The hidden Abs to KLH were revealed by demonstrating increases in anti-KLH activity in sera incubated previously with Fab' fragments, immobilized on plastic microtitre tray wells. Incubation with insoluble Fab' did not influence the quantity of anti-tetanus toxoid (TT) that was detected in these sera. Addition of affinity purified anti-Fab' Abs to samples, previously 'unblocked' by adsorption with immobilized Fab', depressed their anti-KLH activity to levels present before adsorption, but did not change the quantity of Abs to Dermatophytin, Trychophyton, or TT therein. These results suggest that some autoantibodies generically recognized as 'Fab' specific' have properties that are usually considered to be characteristic of autoanti-idiotypes.

Adult↗

PubMed1982

Familial rheumatoid arthritis: a kindred identified through a proband with seronegative juvenile arthritis includes members with seropositive, adult-onset disease.

Segregation of chromosome #6 markers has been studied in a large family, identified by a proband with seronegative, juvenile-onset rheumatoid arthritis, which contains four other individuals with adult-onset rheumatoid arthritis (RA). Two of the adult-onset patients have classical seropositive RA. Sera from two healthy members of this family also contain rheumatoid factors (RF). Six family members had crossovers in the short arm of chromosome #6. Three individuals with recombinants between HLA-B and HLA-D were identified; three others had identifiable crossovers between HLA-D and GLO (Glyoxylase 1). Linkage analysis suggested that susceptibility to RA in this family was influenced by a dominant gene located centromeric to HLA-B. The highest lod score (1.64) was obtained for linkage to GLO at a recombination rate of zero. Inheritance of specific chromosome #6 or Gm immunoglobulin allotype markers did not appear to influence serum RF. These results agree with previous family studies which suggest that acquisition of childhood- and adult-onset RA is influenced by a common disease susceptibility gene, linked to the major histocompatibility gene complex.

Adolescent↗

PubMed1982

Production of antibodies specific for Fc, Fab', and streptokinase-streptodornase in vitro by peripheral blood cells from patients with rheumatoid arthritis and normal donors. Identification of immune complexes in culture supernatants containing hidden antibodies reactive with Fab' fragments of immunoglobulin G.

To study antibody (Ab) biosynthesis in rheumatoid arthritis (RA), the immunoglobulin (Ig)M anti-Fc, anti-Fab', and antistreptokinase-streptodornase (SKSD) produced by peripheral blood lymphocytes (PBL) were measured at intervals from 1 to 19 d in culture. PBL from 17 seropositive patients with active RA and 30 age-matched controls were evaluated. Within the first 24 h, PBL from six of eight patients released >30 ng IgM anti-Fc, even in the absence of pokeweed mitogen (PWM). This early release of Ab was blocked by cycloheximide. With or without PWM, PBL from normal donors did not release IgM anti-Fc until after 3-5 d in vitro. By day 9, unstimulated PBL from seven patients made > 100 ng IgM anti-Fc. Un-stimulated PBL from normals never made >95 ng of this Ab. When PWM was added, PBL from normal donors released as much IgM anti-Fc as was found in RA donor cultures. Paradoxically, addition of PWM to PBL of RA patients suppressed release of IgM anti-Fc in 4 of 17 cases to levels significantly below those found in unstimulated cultures of the same cells. Without PWM, PBL from RA donors frequently failed to make IgM anti-SKSD (P < 0.05 compared with normal donors' cells). With PWM, the quantities of IgM anti-SKSD released were comparable. Fluctuations in IgM anti-Fab' levels during the life-time of these cultures were sufficient to suggest that these Ab may be taken up in immune complexes. This hypothesis was verified by acidifying (pH 3.1) culture supernatants to which (125)I-Fab' had been added previously. The samples were then neutralized (pH 7.6) and 12% polyethylene glycol was added to separate free from antibody-bound (125)I-Fab'. This procedure increased the quantity of (125)I-Fab' precipitated by > 10-fold in some cases. These studies suggest that there are a variety of abnormalities in Ab biosynthesis in RA. These include spontaneous synthesis of comparatively large quantities of IgM anti-Fc, relatively suppressed release of IgM anti-SKSD, and a paradoxical reduction, in some cases, in the biosynthesis of IgM anti-Fc after addition of PWM.

Antibodies, Anti-Idiotypic↗