The Role of Cell Membrane Immunoglobulin in Primate B Lymphocyte Differentiation

Finkelman, Fred D.; Lipsky, Peter E.

doi:10.1111/j.1600-065x.1979.tb00275.x

Cited by 18 publications

(11 citation statements)

References 50 publications

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“…Considerable evidence has been presented demonstrating that B cells may be induced to proliferate extensively, as with anti-immunoglobulin stimulation, without differentiating to produce immunoglobulin (18,19). More recently, the differentiation or maturation of B cells to immunoglobulin production without concomitant proliferation has also been reported in both murine and human systems (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes.

Grayson¹,

Dooley²,

Koski³

et al. 1981

J. Clin. Invest.

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A B S T R A C T The direct effects of steroid hormones on the production of immunoglobulins and DNA synthesis by human T and B lymphocytes was evaluated in cultures of peripheral blood mononuclear cells. As detected by a reverse hemolytic plaque assay, the addition of 0.1 mM to 10 nM hydrocortisone to lymphocytes in culture in the absence of other stimulants or mitogens, resulted in the dramatic induction of immunoglobulin production with responses comparable to those seen in similar cultures stimulated with pokeweed mitogen. Steroid-stimulated immunoglobulin production was first seen after 48 h and peaked at 8-10 d of culture. The production of IgG, IgA, and IgM was induced following incubation with steroid. Glucocorticoids, but not estrogens or androgens, were capable of mediating this effect, and only compounds with affinity for the glucocorticoid receptor were active. The induction of immunoglobulin production was dependent on both T cells and monocytes; cultures depleted of either cell type did not produce immunoglobulin when stimulated with glucocorticoid hormones. Proliferation of B cells or T cells could not be detected by [3H]thymidine incorporation or total cell recovery from steroid-stimulated cultures, even though such cultures demonstrated marked increases in immunoglobulin production. The mechanism responsible for this functional maturation of B cells to become high rate immunoglobulin producing cells is as yet undefined, although it appears to involve more than merely steroid mediated inactivation of suppressor T cells.

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Section: Discussionmentioning

confidence: 99%

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes.

Grayson¹,

Dooley²,

Koski³

et al. 1981

J. Clin. Invest.

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“…The role of sIgD on human B lymphocytes is less clear. A n t i 4 antibodies are reported to show no effect on IgG or IgM production [14] or inhibition of IgG and variable effects on IgM production [13] by mitogen-stimulated tonsil or spleen cells. Thiele et al [16] found that all the IgG production induced by purified protein derivitive of tuberculin (PPD) or lipopolysaccharide (LPS) mitogens was derived from 6precursors in the blood of antigen-boosted donors.…”

Section: Introductionmentioning

confidence: 99%

IgM‐ and IgD‐bearing peripheral blood lymphocytes differentiate to IgM but not IgG or IgA immunoglobulin‐secreting cells

Saiki

Ralph

1982

Eur J Immunol

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Human peripheral blood mononuclear cells were depleted of surface IgM+ or IgD+ cells and assayed for mitogen-induced differentiation to immunoglobulin-secreting cells (ISC) of IgM, IgG and IgA classes. Stimulatory agents included T cell-dependent pokeweed mitogen, B cell mitogen Staphylococcus aureus bacteria strain Cowan I, and a combination of the two which gives uniform, high levels of ISC from all normal donors. Depletion of either IgM- or IgD-bearing B lymphocytes resulted in loss of cells bearing the other Ig class and blocked most of the mitogenic reactivity to anti-IgM and anti-IgD. Proliferative responses to Cowan I in these depleted populations were about 20% that of unfractionated mononuclear cells. Depletion of T cells increased the mitogenic response to Cowan I and to the two antibody preparations, showing that they are T-independent mitogens. Depletion of IgD+ cells caused partial loss of mitogen-induced IgM ISC (22%-60% of unseparated controls) but no loss of IgG or IgA ISC. Depletion of IgM-bearing cells caused complete loss of IgM ISC, but no loss of IgG or IgA ISC. We previously demonstrated that anti-IgM ISC, but no loss of IgG or IgA ISC. We previously demonstrated that anti-IgM antibody blocked mitogen induction of Ig secretion of these three classes in spleen cells, but only IgM secretion in blood mononuclear cells. Together, the results suggest that the majority of cells in normal blood responding to mitogens to mature to IgG or IgA production belong to IgM-, IgD- B cell subjects, in contrast to precursors of secreting cells for these isotypes in the spleen. Thus, these blood precursors appear to be more mature than the corresponding spleen cells.

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“…Both a primary IgM response and a secondary IgG response have been blocked by treatment of the cells with anti-,i (10)(11)(12), suggesting that IgM may be essential in "triggering" these responses. Mitogeninduced secretion of IgM and IgG have been blocked with anti-,u (13)(14)(15) or anti-S (15). However, anti-S did not block a secondary IgG response (12) and, when administered in vivo to rhesus monkeys, markedly increased IgM and IgG synthesis (16).…”

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confidence: 99%

Blocking of primary in vitro antibody responses to thymus-independent and thymus-dependent antigens with antiserum specific for IgM or IgD.

Cambier

Ligler

Uhr

et al. 1978

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

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The effect of anti-M and anti-6 on the primary in vitro IgM response of murine splenocytes to thymus-dependent (trinitrophenylated erythrocytes) and thymus-independent (trinitrophenylated brucella) forms of trinitrophenyl was studied. The results indicate that either anti-M or anti-S can block the response of adult splenocytes to the thymus-dependent antigen. The thymus-dependent responses of neonatal splenocytes that bear a low concentration of IgD were also abrogated by treatment with anti-S. In contrast, anti-,u, but not anti-5, blocked the response of adult splenocytes to the thymus-independent antigen used. These results indicate that both IgM and IgD are receptors required for triggering cells by a thymus-dependent antigen but that only IgM receptors are required for triggering by the thymus-independent antigen used. MATERIALS AND METHODSAntisera. The preparation and specificity of rabbit antimouse Ig (anti-Ig), rabbit anti-,u, and goat anti-rabbit IgThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisemnent" in accordance with 18 U. S. C. §1734 solely to indicate this fact.(GARIg) have been described (17). Rabbit anti-6 was judged to be monospecific by published criteria (18), including: (i) a single peak on sodium dodecyl sulfate/polyacrylamide gel electrophoresis after reaction with a lysate of iodinated splenocytes; (ii) immunofluorescent staining of the predicted numbers of cells from various lymphoid tissues; (iii) inability to stain splenocytes after their treatment with either anti-Ig or allotypic (19) anti-6; and (iv) independent capping of surface molecules on splenocytes with anti-6 and anti-A. Chromatographically purified fractions of normal rabbit serum (NRS), anti-,q, anti-Ig, or a 30% (NH4)2SO4 saturation precipitate of anti-6 was used for in vitro cell culture. The IgG fraction from GARIg was conjugated with fluorescein isothiocyanate (Sigma) (FITC-GARIg) and chromatographed on DEAE-cellulose (Whatman DE52) to give a fraction with molar fluorescein/ protein ratio of 2.6.Capping of Cell Surface Ig. Splenocytes were incubated for 30 min at 4°with NRS or the rabbit antisera described above. Cells were washed and exposed to GARIg (20) for 90 min at 370 in complete medium to achieve capping.Immunofluorescent Staining. Viable cells were prepared and treated with NRS or antisera specific for Ig, ,u, or 6 as described (20 Preliminary experiments had indicated that capping alone with any of the anti-Igs used was ineffective in blocking subsequent immune responses, incubation with anti-Igs only (without prior capping) was marginally effective. Therefore, in the experiments described, control cells were capped with

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The Role of Cell Membrane Immunoglobulin in Primate B Lymphocyte Differentiation

Cited by 18 publications

References 50 publications

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes.

Immunoglobulin production induced in vitro by glucocorticoid hormones: T cell-dependent stimulation of immunoglobulin production without B cell proliferation in cultures of human peripheral blood lymphocytes.

IgM‐ and IgD‐bearing peripheral blood lymphocytes differentiate to IgM but not IgG or IgA immunoglobulin‐secreting cells

Blocking of primary in vitro antibody responses to thymus-independent and thymus-dependent antigens with antiserum specific for IgM or IgD.

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