The effects of a monoclonal anti‐μ chain antiserum on the in vitro growth of normal B cells

Boyd, Andrew W.; Pike, Beverley L.

doi:10.1002/eji.1830120303

Cited by 7 publications

(8 citation statements)

References 26 publications

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“…The effects of Ab binding to Fc receptors has been shown to influence B cell activation by anti-Ig Ab (10,(19)(20)(21). However, it is unlikely that an Fc regionmediated mechanism is responsible for all differences in the mitogenic character of the individual anti-# mAb in this study, since five of those that displayed functional differences were of the same 3"1 isotype.…”

Section: Discussionmentioning

confidence: 80%

Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies.

Rudich¹,

Winchester²,

Mongini³

1985

The Journal of Experimental Medicine

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Seven murine monoclonal antibodies (mAb) with different binding characteristics for human IgM varied markedly in their ability to induce proliferation of T cell-depleted human splenocytes. Two mAb (HB57 and 5D7) that bound to distinct epitopes on IgM were highly effective initiators of B cell proliferation at very low concentrations, in the presence of a T cell factor source. In the absence of T cell supernatant, both HB57 and 5D7 mAbs produced a markedly reduced degree of stimulation at all concentrations. Two additional anti-IgM mAb (VIIIE11 and Mu53) were distinctive in that, even at high concentrations, only limited proliferation was observed compared with the first group of mAb. This proliferation depended on the presence of T cell supernatant. Competitive-binding studies revealed that the epitope recognized by mAb Mu53 may be identical or very proximate to that recognized by HB57. Three other mAb (1G6, XG9, and P24) induced little or no proliferation. 1G6 bound to a unique epitope on the IgM molecule, whereas XG9 shared a determinant with VIIIE11 mAb. Regulatory influences of Fc receptor binding cannot account for all the diversity in proliferation observed with the individual anti-IgM mAb. Markedly augmented proliferation was obtained when B cells were cultured with certain combinations of anti-IgM mAb in the presence of exogenous T cell supernatant. The proliferation induced in the absence of T cell supernatant by high concentrations of mAb mixtures that included 1G6 approached that observed for the same mixtures in the presence of T cell supernatant. The data suggest that certain signals delivered through membrane IgM can bypass the need for T cell supernatant in the activation of human B lymphocytes.

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Section: Discussionmentioning

confidence: 80%

Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies.

Rudich¹,

Winchester²,

Mongini³

1985

The Journal of Experimental Medicine

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“…The F23.1 (mouse anti-TcR Vp8) [15] and E4.2 (rat anti-mouse p) [19] antibodies were affinity purified by protein A chromatography (Pharmacia), and the 30H12 (rat anti-Thy-1.2) [20], 53-6-7.2 (rat anti-Ly-2) [20], F7D5 (mouse anti-Thy-1.2) [21] and GK1.5 (rat anti-L3T4) [22] antibodies were used as dilutions of culture supernatant. E4.2 was conjugated at 1 mg/ml to cyanogen bromide-activated Sepharose 4B (Pharmacia).…”

Section: Antibodiesmentioning

confidence: 99%

A noncognate interaction with anti‐receptor antibody‐activated helper T cells induces small resting murine B cells to proliferate and to secrete antibody

Owens

1988

Eur J Immunol

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Culture of small resting allogeneic B cells (of an irrelevant haplotype) with two clones of T helper (Th) cells that were activated by the F23.1 anti-T cell receptor antibody led to the activation of B cells to proliferate and to secrete antibody. Th cell supernatants by themselves had no effect on resting B cells (even in the presence of intact F23.1 antibody), but could induce antibody secretion by anti-Ig-preactivated B cells. Both F23.1+ clones (E9.D4 and 4.35F2) and one F23.1- clone (D2.2) could synergize with supernatants from activated E9.D4 T cells to induce B cell activation. F(ab')2 fragments of F23.1 induced E9.D4 to activate B cells as efficiently as intact F23.1 and B cell populations that had been incubated with F23.1 were not activated when cultured with E9.D4, although T cells recognized cell-presented F23.1 and were weakly activated. Reduction of the density of F23.1 adsorbed to plastic resulted in weak T cell activation, and these T cells did not induce B cell responses. Haptenated B cell populations, although recognized by E9.D4, were not activated. Separation of T and B cells by a 0.4-micron membrane prevented T-dependent B cell activation, although Th cell-derived B cell-activating lymphokines would be assayed across these membranes. These results suggest a polyclonal noncognate B cell activation that depends on physical contact between B cells and activated T cells. The requirement for a cognate interaction of Th with B cells for the production and delivery of B help can therefore be overcome by activating Th cells with high densities of T cell receptor ligands.

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“…In contrast, we wished to determine whether concentrations of anti-M antibody too low to impede the development of a B cell population with normal mlg receptors could nevertheless functionally impair the cells, creating a population of universally anergic B cells. We developed an in vitro strategy because transplacental transfer of anti-p chain IgG would be inhibited by the large amount of IgM in the maternal circulation, leading to immune complex formation; and intrafetal injections are accompanied by uncertainties relating to leakage into the amniotic fluid.In this paper, we document the effects on maturing B cells of very low concentrations of a monoclonal anti-,s chain antibody, E4, the product ofa rat-murine hybridoma and the preparation and properties of which we have described (12). Adult bone marrow or newborn spleen cells were fractionated in the FACS to obtain mIg-cells, which were cultured in the presence or absence of E4 for a period of 1 or 2 days, allowing many cells to mature into functional B lymphocytes in control cultures (13).…”

mentioning

confidence: 99%

“…In this paper, we document the effects on maturing B cells of very low concentrations of a monoclonal anti-,s chain antibody, E4, the product ofa rat-murine hybridoma and the preparation and properties of which we have described (12). Adult bone marrow or newborn spleen cells were fractionated in the FACS to obtain mIg-cells, which were cultured in the presence or absence of E4 for a period of 1 or 2 days, allowing many cells to mature into functional B lymphocytes in control cultures (13).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clonal anergy: the universally anergic B lymphocyte.

Pike¹,

Boyd²,

Nossal³

1982

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

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The clonal anergy theory of induction of immunological tolerance states that differentiating B lymphocytes that encounter multivalent antigen at the pre-B to B cell transition stage can receive and store a negative signal, which renders them anergic to later triggering stimuli. The theory was tested by using an anti-IL chain monoclonal antibody, E4, as a model tolerogen.The fluorescence-activated cell sorter was used to select B cellfree cell populations from adult murine bone marrow or newborn spleen, and later, to analyze B cell neogenesis in vitro. The presence of E4 at 21 jg/ml was required to impede the development of normal numbers of B cells with full receptor status. The subsequent capacity of these B cells to respond in vitro to mitogens was assessed in a filler-cell free microculture system that allows single B cells to proliferate and differentiate. Concentrations of E4 far below those required to affect B cell neogenesis had profound inhibitory effects on the subsequent functional capacity of the B cells. In fact, 10-3 jig/ml of E4 markedly impaired both proliferation and antibody formation, and 10' jig/ml, which had no effect on Ig receptor development, abrogated functional ca- It is now well established that immature cells of the B lymphocyte lineage can be rendered immunologically tolerant by certain multivalent antigens both in vitro and in vivo (1-8). Recently, we provided evidence that the stage at which the cell displayed its greatest sensitivity to negative signaling was that of first emergence of the surface membrane immunoglobulin (mIg) receptors, that is, during the pre-B to B cell transition (7). It is possible to introduce tolerogens into the tissues of the developing fetus by transplacental transfer (6) and thus ensure interaction between lymphoid cells and tolerogen at the first appearance of specific antigen binding receptors. When fluoresceinated human gamma globulin (FLU-HGG) was injected into mice at 14.5 days ofgestation, effective B cell tolerance was induced with doses far lower than those required to reduce the number of FLU-specific antigen-binding B cells in the offspring (8). In other words, B lymphocytes expressing a normal range of FLU-binding avidities appeared to emerge from the pre-B cell pool in normal numbers, but were incapable of giving rise to anti-FLU antibody-forming cell (AFC) clones when challenged with a B cell mitogen or a T lymphocyte-independent antigen. This suggested that interaction between the newly emerged anti-FLU receptors and antigen had neither impeded the subsequent development of a standard complement of mIg nor directly led to the death of the anti-FLU B cell. Rather, the cell, though still alive and capable ofbinding antigen, appeared to have received some signal rendering it incapable of responding to appropriate triggering stimuli. We termed this phenomenon clonal anergy.This conclusion was dependent on a technology that enumerated and characterized FLU-binding B cells, by counting cells adhering specifically to thin layers of hapten...

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The effects of a monoclonal anti‐μ chain antiserum on the in vitro growth of normal B cells

Cited by 7 publications

References 26 publications

Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies.

Human B cell activation. Evidence for diverse signals provided by various monoclonal anti-IgM antibodies.

A noncognate interaction with anti‐receptor antibody‐activated helper T cells induces small resting murine B cells to proliferate and to secrete antibody

Clonal anergy: the universally anergic B lymphocyte.

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