Depressed in Vitro B—Lymphocyte Differentiation in Systemic Lupus Erythematosus

Bobrove, Arthur M.; Miller, Philip

doi:10.1002/art.1780200705

Cited by 38 publications

(9 citation statements)

References 31 publications

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“…Indeed, using monoclonal antibodies reactive with monocytic cells we could confirm a recent report showing higher concentrations of monocytes in Ficoll-Hypaque MNC suspensions from patients with HD than in controls (20 (27)(28)(29), and antibodies against Epstein-Barr and other viral antigens (30,31) in patients with HD. Depressed Ig synthesis after stimulation with PWM, associated with enhanced spontaneous IgG synthesis, has also been reported in patients with systemic lupus erythematosus (32,33) and Henoch-Sch6nlein purpura (34) and attributed to an excessive B cell stimulation in vivo (35)(36)(37)(38).…”

Section: Resultsmentioning

confidence: 85%

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

Romagnani¹,

Prete²,

Maggi³

et al. 1983

J. Clin. Invest.

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A B S T R A C T The immunoglobulin-synthesizing activities of peripheral blood mononuclear cells from 57 untreated patients with Hodgkin's disease and 47 normal subjects were compared. Cumulative amounts of IgM and IgG synthesized and secreted by unstimulated and pokeweed mitogen-stimulated cells over a 7-d period were determined in a solid-phase radioimmunoassay. Synthesis of IgM in unstimulated cultures and of both IgM and IgG in cultures stimulated with pokeweed mitogen was markedly reduced in patients with Hodgkin's disease, whereas the mean level of the spontaneous IgG synthesis was enhanced. The degree and frequency of in vitro abnormalities were not influenced by disease stage or histology.Depression of pokeweed mitogen-induced immunoglobulin synthesis did not correlate with excessive number of monocytes and it was unaffected by removal of phagocytic cells or addition to the cultures of monocytes from normal individuals. On the other hand, monocytes isolated from blood of patients with Hodgkin's disease were even more effective than normal monocytes in supporting pokeweed mitogen-induced immunoglobulin synthesis by normal phagocyte-depleted mononuclear cells. Synthesis of both IgM and IgG induced by pokeweed mitogen remained subnormal after addition to patient B cell cultures of autologous irradiated T cells or allogeneic normal T lymphocytes. T cells from patients with Hodgkin's disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkin's disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells

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Section: Resultsmentioning

confidence: 85%

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

Romagnani¹,

Prete²,

Maggi³

et al. 1983

J. Clin. Invest.

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“…These include autoantibodies, such as DNA, and antibodies to specificities thought to be unrelated to self antigens such as trinitrophenyl (23)(24)(25)(26). It is also reported that lymphocytes from SLE patients had a markedly depressed in vitro response to PWM with regad to Ig synthesis (21,27). Similarly, the A,G,C,T-specific antibody response by SLE lymphocytes was decreased following stimulation with PWM.…”

Section: Resultsmentioning

confidence: 99%

In vitro nucleoside specific immune response by lymphocytes from systemic lupus erythematosus.

Morimoto¹,

Steinberg²,

Schlossman³

et al. 1983

J. Clin. Invest.

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“…Indeed, low or normal levels of IL-1 (20,21), IL-2 (21,22), interferon (23), and B cell growth and differentiation factors (24) in vitro have all been reported, suggesting that these specific lymphokines are not directly involved in B cell hyperactivity. Impaired B cell responses to mitogen stimulation (25) and preparations containing B cell differentiation factor (26) have also been described, which implies that the responsiveness of SLE B cells to these stimuli is impaired. The ACS-induced differentiation of B cells described in the present study is therefore a novel finding which is directly relevant to understanding B cell hyperactivity.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of b cell differentiation by adherent mononuclear cells in systemic lupus erythematosus

Jandl

Adirim

Schur

1987

Arthritis & Rheumatism

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We studied B cell proliferation and differentiation in response to factors released by adherent monocytes in patients with systemic lupus erythematosus (SLE). Adherent cell supernatants (ACS) were added to peripheral blood mononuclear cells, and the effects on IgG synthesis, the number of Ig-secreting cells (ISC), and proliferation were determined. Exposure of SLE mononuclear cells to autologous ACS caused an increase (approximately twofold) in IgG production and ISC numbers. In contrast, exposure of normal mononuclear cells to autologous ACS did not significantly increase IgG production or ISC numbers. Addition of SLE ACS to cultures of normal mononuclear cells did not stimulate ISC production. There was no significant level of 'H-thymidine uptake by cultures of SLE or normal mononuclear cells in response to either SLE or normal ACS. In the presence of an excess number of autologous T cells, ACS stimulation of IgG synthesis was further enhanced. These findings indicate that adherent monocytes contribute to B cell hyperactivity in SLE by stimulating B cell differentiation. SLE mononuclear cells appear to be more responsive to ACS stimulation than are normal mononuclear cells. 'The response of normal resting B cells to foreign antigens is a complex sequence of events, which involves activation, proliferation, differentiation, and immunoglobulin secretion. The importance of an orderly and controlled progression through this sequence is emphasized by the extraordinary array of regulatory cells and lymphokines that are capable of acting on various stages of this pathway. Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with excessive B cell activity. Specifically, large amounts of immunoglobulin and numerous autoantibodies are secreted by SLE B cells, and the proportion of circulating B cells that spontaneously secrete Ig is markedly increased in SLE patients (1,2). Other abnormalities of B-lineage cells that have been reported in SLE patients include increased numbers of circulating immunoblasts (3), cells containing intracyloplasmic Ig (4), low numbers of circulating IgD-bearing cells (3, and increased surface Ig (sIg) negative, Ig-secreting cells (ISC) (6).Together these findings suggest that there are substantial abnormalities of the circulating B cell population in patients with SLE. Circulating immune complexes result from B cell hyperactivity and appear to cause certain of the pathologic manifestations of the disease (7). In an effort to understand the basis of SLE B cell hyperactivity, numerous studies have measured lymphokine levels and regulatory T cell and monocyte functions in vitro and in vivo. While many abnormalities have been found, it remains unclear at what stage in the maturation sequence these immunoregulatory abnormalities might contribute to SLE B cell hyperactivity.Recent studies at our laboratory have provided a unique opportunity to study SLE B cell proliferation

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Depressed in Vitro B—Lymphocyte Differentiation in Systemic Lupus Erythematosus

Cited by 38 publications

References 31 publications

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

In vitro nucleoside specific immune response by lymphocytes from systemic lupus erythematosus.

Stimulation of b cell differentiation by adherent mononuclear cells in systemic lupus erythematosus

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