Enhancement of Human Lymphocyte Transformation by Aggregated Human Gamma Globulin

Kinsella, Thomas

doi:10.1172/jci107648

Cited by 14 publications

(6 citation statements)

References 24 publications

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“…Lyophilized human Cohn fraction I1 (Squibb, New York, NY) was dissolved in RPMI 1640 medium and sterilized with a 0.45 km pore Millipore filter (Millipore Co, Bedford, MA). Aggregation was carried out by heating at 56°C for 30 minutes (9), and protein concentration was adjusted to a concentration of 10 mg/ml (12). The Cohn FII solution contained IgG but no IgM, IgA, or albumin by immunodiffusion and immunoelectrophoresis studies.…”

Section: Methodsmentioning

confidence: 99%

Enhancement of in vitro immunoglobulin synthesis of rheumatoid lymphocytes by aggregated human gamma globulin

Yamasaki

Ziff

1977

Arthritis & Rheumatism

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In vitro immunoglobulin synthesis by lymphocytes of patients with rheumatoid arthritis (RA) was enhanced by the addition of heat‐aggregated human IgG. Stimulation occurred in the presence of fresh seropositive autologous plasma and was abolished by heat inactivation. By contrast, no significant stimulation was induced in lymphocytes from patients with miscellaneous arthritides and normal subjects cultured in the presence of either fresh autologous plasma or fresh normal AB serum. Although stimulation of RA lymphocytes did not occur in the presence of fresh AB serum, it did when purified IgM rheumatoid factor was added to this serum. These results suggest that immune complexes formed between aggregated IgG and rheumatoid factor in the presence of complement stimulate immunoglobulin synthesis in the peripheral blood lymphocytes of patients with RA.

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Section: Methodsmentioning

confidence: 99%

Enhancement of in vitro immunoglobulin synthesis of rheumatoid lymphocytes by aggregated human gamma globulin

Yamasaki

Ziff

1977

Arthritis & Rheumatism

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“…<dFðt1sÞdFðtÞ > <FðtÞ> 2 (1) For fluorescence intensity fluctuations arising from translational diffusion, the time-dependent part of the correlation function is given by:…”

Section: Gðsþ5mentioning

confidence: 99%

“…Globulins are a class of globular proteins (molecular weight ∼ 150 kDa) categorized as alpha, beta, and gamma globulins according to increasing size. Some of the gamma globulins are immunologically active and are called immunoglobulins (IgG's) . The structure of IgG comprises of four polypeptide chains: two identical light chains (molecular weight 22–23 kDa) and two identical heavy chains (molecular weight 50–70 kDa) .…”

Section: Introductionmentioning

confidence: 99%

“…In this work, we have studied the aggregation kinetics of one such functional aggregate, namely that formed by IgG. In vitro studies suggest that IgG, particularly in aggregated form, combine with rheumatoid factor (RF) to form a complex C and initiates the blood complement sequence, producing various phlogistic mediators . Various studies provide evidence that aggregation of IgG leads to exposure of specific groups, which were initially unavailable in the native protein for reacting with RF.…”

Section: Introductionmentioning

confidence: 99%

“…In vitro studies suggest that IgG, particularly in aggregated form, combine with rheumatoid factor (RF) to form a complex C and initiates the blood complement sequence, producing various phlogistic mediators. [1][2][3][4] Various studies provide evidence that aggregation of IgG leads to exposure of specific groups, which were initially unavailable in the native protein for reacting with RF. Aggregation of IgG is postulated to proceed via rupture of interchain disulfide bonds, which in turn causes intermolecular bridging leading to aggregate formation and to the likely exposure of new chemical groups having affinity for RF.…”

Section: Introductionmentioning

confidence: 99%

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Intermolecular disulfide bond formation promotes immunoglobulin aggregation: Investigation by fluorescence correlation spectroscopy

2014

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Protein aggregation generally results from association between hydrophobic regions of individual monomers. However, additional mechanisms arising from specific interactions, such as intermolecular disulfide bond formation, may also contribute to the process. The latter is proposed to be the initiating pathway for aggregation of immunoglobulin (IgG), which is essential for triggering its immune response. To test the veracity of this hypothesis, we have employed fluorescence correlation spectroscopy to measure the kinetics of aggregation of IgG in separate experiments either allowing or inhibiting disulfide formation. Fluorescence correlation spectroscopy measurements yielded a diffusion time (τ(D)) of ∼200 µsec for Rhodamine-labeled IgG, corresponding to a hydrodynamic radius (R(H)) of 56 Å for the IgG monomer. The aggregation kinetics of the protein was followed by monitoring the time evolution of τ(D) under conditions in which its cysteine residues were either free or blocked. In both cases, the progress curves confirmed that aggregation proceeded via the nucleation-dependent polymerization pathway. However, for aggregation in the presence of free cysteines, the lag times were shorter, and the aggregate sizes bigger, than their respective counterparts for aggregation in the presence of blocked cysteines. This result clearly demonstrates that formation of intermolecular disulfide bonds represents a preferred pathway in the aggregation process of IgG. Fluorescence spectroscopy showed that aggregates formed in experiments where disulfide formation was prevented denatured at lower concentration of guanidine hydrochloride than those obtained in experiments where the disulfides were free to form, indicating that intermolecular disulfide bridging is a valid pathway for IgG aggregation.

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Altered lymphocyte reactivity in rheumatoid arthritis

Silverman

Johnson

Vaughan

et al. 1976

Arthritis & Rheumatism

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Blastogenic transformation of peripheral lymphocytes with phytohemagglutinin (PHA), conconavalin A (Con A), and pokeweed mitogen (PWM) was studied in 29 patients with rheumatoid arthritis (RA). The PHA response was depressed in a subgroup of RA patients with erosive disease. The Con A response was also depressed and paralleled the PHA response. The PWM response was not depressed. These results lend support to the hypothesis of a functional defect of cellular immunity in RA. It was shown that lymphocyte responsiveness to a single mitogen concentration is not an adequate assessment of the overall responsiveness of the lymphocytes tested.

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Enhancement of Human Lymphocyte Transformation by Aggregated Human Gamma Globulin

Cited by 14 publications

References 24 publications

Enhancement of in vitro immunoglobulin synthesis of rheumatoid lymphocytes by aggregated human gamma globulin

Enhancement of in vitro immunoglobulin synthesis of rheumatoid lymphocytes by aggregated human gamma globulin

Intermolecular disulfide bond formation promotes immunoglobulin aggregation: Investigation by fluorescence correlation spectroscopy

Altered lymphocyte reactivity in rheumatoid arthritis

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