Regulation of Human B Cell Activation

Geha, Raif S.

doi:10.1111/j.1600-065x.1979.tb00281.x

Cited by 36 publications

(10 citation statements)

References 97 publications

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“…The above data are in agreement with previous observations on human and mouse cells [37][38][39][40][41] showing that restriction in antibody production is confined solely at the level of the interaction between T cells and macrophages. However, opposite results have been reported by others [28,29,[42][43][44] and owing to the compIexities of the experimental systems, there are no simple explanations for the discrepancies. It is possible that in various systems different responses were given by distinct B cell subsets [45] (some of which were only restricted to histocompat-ible cooperation) or by B cells at different stages of maturation [36].…”

Section: Discussioncontrasting

confidence: 64%

Human T cell lines with antigen specificity and helper activity

1982

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Human T blasts, obtained by stimulation of peripheral blood mononuclear cells (PBM) with tetanus toxoid, diphtheria toxoid or Candida albicans, were expanded in long-term culture using alternate periods of antigen restimulation and growth in media containing interleukin 2. The cells gave a proliferative response only to the antigen originally used for stimulation. Such as response was strictly dependent upon the presence of autologous but not of allogeneic mitomycin C-treated mononuclear cells. When added to autologous PBM depleted of E-rosetting cells together with the specific antigen, the T blasts induced a polyclonal proliferation and differentiation of B cells. Allogeneic B cells were activated by antigen-stimulated T blasts only in the presence of irradiated mononuclear cells autologous to the responding T blasts. The above responses seemed not to be regulated solely by the release of soluble factors; apparently cell to cell interactions had to take place to obtain an efficient B cell activation.

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Section: Discussioncontrasting

confidence: 64%

Human T cell lines with antigen specificity and helper activity

1982

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“…ate in response to UDTT, and the proliferative response to [25][26][27] suggests that such a mechanism could be operative, they piovided no information as to the contribution of these determinants to the overall proliferative response of the human T cell to TT antigen. The most innovative aspect of the present study was the demonstration that the T cells which proliferated in response to TT essentially overlapped with those that proliferated in response to UDTT.…”

Section: Discussionmentioning

confidence: 99%

Nature of the immunogenic moiety recognized by the human T cell proliferating in response to tetanus toxoid antigen

1981

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This study was undertaken to investigate the nature of the immunogenic moiety recognized by the human T cell which proliferates in response to tetanus toxoid (TT) antigen. Immunosorbent-purified anti-TT IgG antibodies failed, even when added in great excess, to inhibit T cell proliferation in response to TT. Urea-denatured (UD) TT antigen containing less than 1% native TT, as assessed by its reactivity with antibodies raised against native TT, triggered proliferation in T cells to an extent equal to that seen with native TT. The proliferative response to UDTT was seen only in T cells obtained from donors immune to TT and was inhibited by antisera to DRw antigens of the cell donor. T cells responding to TT and to UDTT essentially overlapped because exposure to 5'-bromo-2-deoxyuridine and light of T cells prestimulated with TT or UDTT abolished the specific response to both forms of the TT antigen but not to phytohemagglutinin or to Monilia antigen. It is concluded that proliferating human T cells recognize determinants which differ from those that elicit an antibody response and which may arise as a result of antigen processing by macrophages. The implications of these present results on the nature of the human T cell receptor for antigen are discussed.

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“…Thus, an in vitro model of antigen induction of antigen-specific antibody synthesis in human peripheral blood mononuclear cells has been demonstrated and should prove useful in exploring the mechanisms of human B cell activation and immunoregulation. (8,9). Human antigen-specific plaqueforming-cell assays have been reported (10)(11)(12); however, results in these systems have been inconsistent among various laboratories (1,2).…”

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confidence: 99%

Antigen-induced in vitro antibody production in humans: a model for B cell activation and immunoregulation.

Volkman¹,

Lane²,

Fauci³

1981

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

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The precise events associated with B cell activation in humans are a subjectofintense investigation. It has been difficult to develop an in vitro model of antigen-specific triggering of antibody synthesis by human peripheral blood mononuclear cells that is independent of exogenous, mitogens. In the present study a sensitive and reproducible culture system and enzymelinked immunosorbent assay have been established wherein antigen alone is used to trigger antigen-specific antibody synthesis by mononuclear cells from subjects immunized to keyhole limpet hemocyanin (KLH (1, 2). Recent studies using a radioimmunoassay have demonstrated antigen-induced triggering of specific antibody responses in peripheral blood mononuclear cells of individuals who had experienced natural infection with influenza virus (13). The present study describes a highly sensitive and reproducible system for the antigen-induced triggering and measurement of specific antibody production by peripheral blood B cells of normal subjects who had been immunized in vivo with the soluble antigen keyhole limpet hemocyanin (KLH). In addition, it examines the roles of antigen and PWM in the in vitro induction of specific and polyclonal antibody synthesis, as well as the phenomenon ofantigen-specific suppression.MATERIALS AND-METHODS Immunization. Normal human subjects received a primary subcutaneous immunization of 5 mg of KLH (Calbiochem, La Jolla, CA) followed by a 2-week booster immunization. Low levels of anti-KLH antibodies were present in the sera of all subjects prior to immunization, as has been previously reported (14). After booster immunization, a 20-to 50-fold increase of IgM and IgG anti-KLH antibodies was noted in the sera. In vitro studies were performed approximately 2 weeks after the booster immunization.Cell Separation and Culture Conditions. Human peripheral blood mononuclear cells were separated by Hypaque/Ficoll gradient centrifugation and cultured in RPMI-1640 medium supplemented with gentamicin at 0.01 mg/ml, 2 mM. L-glutamine, trypticase soy broth at 0.03 mg/100 ml, and 10% heatinactivated fetal calf serum (Flow Laboratories, McLean, VA The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

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Regulation of Human B Cell Activation

Cited by 36 publications

References 97 publications

Human T cell lines with antigen specificity and helper activity

Human T cell lines with antigen specificity and helper activity

Nature of the immunogenic moiety recognized by the human T cell proliferating in response to tetanus toxoid antigen

Antigen-induced in vitro antibody production in humans: a model for B cell activation and immunoregulation.

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