Modulatory effects on immunoglobulin synthesis and secretion by lymphocytes from immunodeficient patients.

Schwartz, Stanley A.; Choi, Yong Sung; Shou, Lien; Good, Robert A.

doi:10.1172/jci108742

Cited by 53 publications

(18 citation statements)

References 21 publications

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“…Waldmann et al (1) have shown that suppressor T-cells from immunodeficient patients are capable of inhibiting PWM-stimulated differentiation of B lymphocytes to produce all classes of Ig. Studies from our laboratories have also demonstrated major shifts in total Ig synthesis, including profound enhancement, in coculture experiments with PBL from normal donors and patients with hypogammaglobulinemia (31). By contrast, however, other investigators have demonstrated highly restricted suppressor activity, including suppression of specific Ig allotypes (11,12), idiotypes (13,14), class (15), and antibodies (16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 94%

“…With regard to these latter effects, very little or no cross-matching at the major histocompatibility complex is required for their expression. We have already demonstrated that naturally occurring suppressor cell activity, which can inhibit Ig synthesis but not proliferative responses by allogeneic donor PBL, is present in the mononuclear leukocyte fraction of peripheral blood from certain hypogammaglobulinemic patients with primary immunodeficiencies (31). This activity compares with the suppressor effect generated by preculture of normal lymphocytes, but contrasts with the wide-ranging activities of Con A-induced suppressor cells, which appear to have the capacity to inhibit both T-and B-lymphocyte-associated activities.…”

Section: Discussionmentioning

confidence: 99%

“…Lectin-activated suppressor cells from healthy donors, however, inhibited cellmediated lysis, but did not affect responses to allogeneic stimuli (7). Studies that demonstrated suppression of Ig synthesis using lymphocytes from hypogammaglobulinemic patients with primary immunodeficiencies failed to exhibit any significant concomitant effect on proliferative responses (31).…”

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confidence: 98%

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Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Schwartz¹,

Shou²,

Good³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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Concanavalin A (Con A)treated peripheral blood lymphocytes from healthy volunteer donors have been shown to suppress proliferative responses associated with thymusderived lymphocytes (T-cells). The present investigations demonstrate that peripheral blood lymphocytes incubated with Con A for 48 hr can abrogate pokeweed mitogen-stimulated differentiation of bone-marrow-derived (B) lymphocytes to immunoglobulin-synthesizing and -secreting plasma cells. This effect was manifested when washed Con A-treated peripheral blood lymphocytes were added to pokeweed mitogen-stimulated cocultures containing fresh autologous or allogeneic mononuclear cells, and it did not appear to involve cytotoxicity. Parallel control cultures consisting of mononuclear leukocytes incubated for 48 hr in the absence of Con A also had immunoglobulin suppressor activity in mixing experiments. This effect, however, was most pronounced when preincubated cells were added to fresh autologous pokeweed mitogen-stimulated peripheral blood lymphocytes. Cell mixtures containing peripheral blood lymphocytes incubated in the absence of Con A plus fresh allogeneic lymphocytes demonstrated a spectrum of immunoregulatory effects ranging from suppression to enhancement of pokeweed mitogen-stimulated immunoglobulin synthesis and secretion. Several functional subclasses of suppressor cells that reflect varying levels of specific activity have thus been demonstrated in human beings. Moreover, a degree of genetic identity appears to be required for the expression of "weak" immunoregulatory influences.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 98%

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Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Schwartz¹,

Shou²,

Good³

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…Deficiencies in the capacity of CVI cells to secrete Ig, assayed in vitro (1)(2)(3)(4)(5), and the variable-to-low numbers of plasmacytes in; lymphoid tissues (6) demonstrate a profound defect in B-cell maturation in this disease. One or more defects in B cells are considered to be the primary cause of the disease in many cases of CVI (1,3,5).…”

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confidence: 99%

Three distinct stages of B-cell defects in common varied immunodeficiency.

Saiki¹,

Ralph²,

Cunningham‐Rundles³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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108

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B-lymphocyte function of 15 patients with primary common varied immunodeficiency or related disease were examined. All patients had low serum levels of IgM, IgG, and IgA, but 12 of 15 patients had nearly normal numbers of peripheral blood B lymphocytes. Mononuclear cells and B cells from peripheral blood were assayed for B-cell mitogenic responses to anti-Ig mu chain antibodies or to Staphylococcus aureus strain Cowan I (referred to as Cowan I), and for differentiation to Ig-secreting cells of IgM, IgG, and IgA classes in the presence of Cowan I and pokeweed mitogen or T-cell factor. The patients all showed profound B-cell defects in one or more of the assays and could be divided into three approximately equal groups based on their responses. The first group showed normal proliferation in response to the two B-cell mitogens and near normal numbers of IgM-secreting cells but no IgG- or IgA-secreting cells. B cells in the second group showed proliferative responses to Cowan I or anti-mu, but no differentiation to Ig-secreting cells. The third group had no B-cell proliferative responses or differentiation in our assays. In several patients from each group, (i) helper T cells were functional in Ig-secreting-cell responses with purified normal B cells, (ii) patient T cells did not significantly suppress formation of Ig-secreting cells by normal cells in coculture, and (iii) removal of T cells with addition of T-cell-replacing factor, or partial removal of monocytes, did not alleviate any of the defects. These studies show that primary B-cell defects in common varied immunodeficiency occur at several levels, probably representing blocks at different stages of differentiation.

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“…The function of only one pool of lymphocytes is being tested. Although PWM has been used previously to explore the cellular aberrations of patients with a variety of immune disorders (15,17,19,26,(28)(29)(30)(31)(32), there is only limited information to indicate that a defective B-cell response to this substance is paralleled by a diminished response of these cells to antigenic challenge (17). It is also apparent that the demonstration of a poor antibody response to antigen- specific challenge would be the critical observation.…”

Section: Discussionmentioning

confidence: 99%

Diminished synthesis of immunoglobulin by peripheral lymphocytes of patients with idiopathic membranous glomerulonephropathy.

Ooi¹,

Ooi²,

Hsu³

et al. 1980

J. Clin. Invest.

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Modulatory effects on immunoglobulin synthesis and secretion by lymphocytes from immunodeficient patients.

Cited by 53 publications

References 21 publications

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Suppression of immunoglobulin synthesis and secretion by peripheral blood lymphocytes from normal donors.

Three distinct stages of B-cell defects in common varied immunodeficiency.

Diminished synthesis of immunoglobulin by peripheral lymphocytes of patients with idiopathic membranous glomerulonephropathy.

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