Regulatory Mechanism of Reagin Production in Mice at the T Cell Level

Takatsu, Kiyoshi; Tominaga, Akira; Hamaoka, Toshiyuki; Kitagawa, Masayoshi

doi:10.1111/j.1348-0421.1979.tb00542.x

Cited by 14 publications

(22 citation statements)

References 30 publications

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“…While no consensus exists about the respective roles ofthe various growth factors capable of affecting B lymphocytes (6)(7)(8)(9)(10)(23)(24)(25)(26)(27)(28)(29)(30)(31), much of the literature on "T-independent" B-cell activation (e.g., ref. 8) supports a scheme shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

“…At this stage, the cell is postulated to display receptors for one or more B-cell growth factors, which drive the cell into active cycle. After an undefined number of divisions, the cells are postulated to display receptors for one or more differentiation factors, which encourage differentiation towards active secretory status (6,8,(23)(24)(25)(26)29).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin 1 can act as a B-cell growth and differentiation factor.

Pike¹,

Nossal²

1985

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

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Splenic B lymphocytes specifically reactive to the hapten fluorescein (FLU) were prepared from nonimmune adult mice by affinity fractionation on hapten-gelatin. These FLU-specific B cells were cultured as single cells or in small numbers in 10-ul wells either in the absence of any feeder, filler, or accessory cell or in the presence of 3T3 fibroblasts acting as filer cells. A selected batch ofa "T-cell-independent" antigen, FLU-Ficoll, which induces growth and differentiation only in the presence of lymphokines or cytokines acting as B-cell growth and differentiation factors (BGDF), was used as the antigenic stimulus. It was found that murine interleukin 1 prepared by recombinant DNA technology was an effective, although weak, BGDF when acting with antigen on B cells cultured either under filler cell-free conditions or in the presence of 3T3 cells. When the murine interleukin 1 was used in combination with recombinant human interleukin 2, itself a weak but effective BGDF in the system, an additive effect was observed. The results challenge the notion that interleukin 1 is exclusively or even primarily an activating cytokine. This system, in which pure factors are able to act with specific antigen on single hapten-specific B cells, will prove helpful for the further dissection of the respective roles of the various factors that can act on B cells.The important macrophage-derived growth-regulatory molecule interleukin 1 (IL-1) (1) has recently been produced in pure form through recombinant DNA technology (2). Ever since the description of IL-1 as a lymphocyte-activating factor (3, 4), its bioactivity has been assumed to relate primarily if not exclusively to early events in the activation of a resting, Go, cell. For example, IL-1 is seen as a cofactor required for concanavalin A to exert its activating effects on T lymphocytes (5) with concomitant expression of IL-2 receptors, after which IL-2 is seen as the only growth factor required for further proliferation of the T-cell clone. IL-1 has also been implicated in the activation of B lymphocytes (6-10), though in this instance, some work has suggested that it acts later than another postulated activating factor, B-cellstimulating factor 1 (BSF-1) (6).We have reported (11-14) a system in which normal murine B lymphocytes, preselected on the basis of their antigen specificity, are able to be stimulated to proliferate and differentiate to immunoglobulin secretion status when cultured singly in the presence of antigen and a source of B-cell growth and differentiation factors (BGDF). Under these conditions, the B cell itself is the only possible target for the action of antigen and factors. In the belief that this system was ideal for testing various purified factors for bioactivity on B cells, we have used it to assess the bioactivity of murine IL-1, prepared by recombinant DNA technology (r-mu-IL-1). The results show IL-1 to have a combination of bioactivities, including the promotion of both growth and differentiation of B cells. Moreover, when filler cells ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interleukin 1 can act as a B-cell growth and differentiation factor.

Pike¹,

Nossal²

1985

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

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“…Cells of various T-cell hybridomas, including the cloned subline of B151, that produce TRF (5) were cultured at 1 x 105 per ml for 48 hr. Culture SN was filtered and aliquots were stored at -700C.…”

Section: Methodsmentioning

confidence: 99%

“…The T-cell-derived lymphokine, T-cell-replacing factor (TRF), was initially described as a factor that induces terminal differentiation of late-developing B cells to immunoglobulin-secreting cells (3)(4)(5)(6). The establishment of a TRF-producing T-cell hybrid B151K12 (B151), which did not secrete any detectable levels of other B-cell stimulatory lymphokines, enabled us to demonstrate that TRF was a lymphokine distinct from interleukins 1, 2, and 3 (IL-1, IL-2, IL-3), B-cell-stimulatory factor type 1 (BSF-1) (interleukin 4, IL-4), and interferon-y (IFN-y) (5,6). Purified TRF from the hybridoma B151 stimulates the differentiation of activated normal B cells and neoplastic B-cell leukemias such as BCL1 cells into immunoglobulin-secreting cells.…”

mentioning

confidence: 99%

Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes.

Takatsu¹,

Kikuchi²,

Takahashi³

et al. 1987

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

117

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We describe an interleukin, termed interleukin 5, that is the recombinant product previously referred to as T-cell-replacing factor (TRF), B-cell growth factor II (BCGF II), or killer-helper factor (KHF). TRF has been defined as a T-cell-derived lymphokine that acts on activated B cells as a B-cell differentiation factor. We have previously demonstrated that TRF is identical to BCGF II and induces expression of receptors for interleukin 2 (IL-2) on activated B cells. We also have reported that KHF can induce not only expression of IL-2 receptors on peanut agglutinin-binding (PNA+) thymocytes but also generation of cytotoxic T lymphocytes (CTL) in PNA' thymocytes in the presence of IL-2. We show here that culture supernatants of T-cell hybridomas that produce TRF as well as TRF purified by high-pressure liquid chromatography (HPLC-TRF) have KHF activity and generate CTL in PNA+ thymocytes in the presence of stimulator cells and IL-2. Moreover, translation products (recombinant TRF) of Xenopus oocytes injected with cDNA encoding for murine TRF (BCGF II) also exert KHF activity. A rat monoclonal anti-TRF antibody TB13 can block generation of CTL by HPLC-TRF or recombinant TRF. These results indicate that TRF acts not only on B cells as BCGF II but also on PNA+ thymocytes as KHF. In view of the diverse activities and targets of TRF, we propose that TRF refers to a different interleukin, interleukin 5.

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“…The problems relating to the nomenclature of the interleukins and their mechanism of action have been the subjects of numerous recent reviews (Kishimoto, 1985(Kishimoto, , 1987Hamaoko & Ono, 1986;Paul & Ohara, 1987;Kishimoto & Hirano, 1988;Sideras, Noma & Honjo, 1988;Sehgal, Grieninger & Tosato, 1989). All ofthe factors are Tcell derived, antigen non-specific in their activity and genetically non-restricted in their capacity to activate the B cells into immunoglobulin-synthesizing and -secreting cells (Takatsu et al, 1980;Nakanishi et al, 1984;Kishimoto, 1985;Sideras et al, 1988). Kishimoto (1985) proposed that the interleukins be categorized into three groups on the basis of their activity: (i) the interleukins that activate the resting B cells; (ii) those that stimulate proliferation of the activated B cells; and (iii) those that induce final differentiation of the activated B cells into immunoglobulin-synthesizing/ secreting cells.…”

Section: Discussionmentioning

confidence: 99%

Cells and mediators which participate in immunoglobulin synthesis by human mononuclear cells. III. Null cells secrete a factor(s) (human immunoglobulin synthesis/secretion-facilitating factor) that can replace the null cells in the synthesis of immunoglobulin by cultured B cells

Taylor

Jodouin

Richter

1990

Clinical and Experimental Immunology

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SUMMARYIn the accompanying communication, it was demonstrated that the null cells, the TM cells, monocytes and PWM are all obligatory participants in the synthesis and secretion of immunoglobulins by human B cells in culture. Here we demonstrate that the null cells secrete a factor, referred to as human immunoglobulin synthesis/secretion-facilitating factor (HISFF) that can replace the null cells in the cultures. HISFF is distinct from the known T cell-derived interleukins. HISFF functions in an HLAunrestricted fashion since it can facilitate the synthesis and secretion of immunoglobulins by allogeneic B cells. The null cells cultured with T^ helper cells and PWM required monocytes in the culture in order to secrete HISFF. Furthermore, B cells cultured with TM cells in medium containing HISFF, monocyte-derived factors and PWM nevertheless required monocytes in order to respond to the HISFF signal. Thus, the monocyte plays a pivotal role in the secretion of and response to HISFF. Normal levels of immunoglobulin were synthesized even when HISFF was added to the cultures of B cells, TM cells and monocytes, in the presence of PWM, as late as day 6 of the 7 day culture. We conclude that the null cells participate in immunoglobulin synthesis by the B cells by secreting a soluble mediator, HISFF, capable of replacing the null cells in the culture; and that the HISFF signal is the last signal received by the B cell before it begins to synthesize and secrete immunoglobulins.

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Regulatory Mechanism of Reagin Production in Mice at the T Cell Level

Cited by 14 publications

References 30 publications

Interleukin 1 can act as a B-cell growth and differentiation factor.

Interleukin 1 can act as a B-cell growth and differentiation factor.

Interleukin 5, a T-cell-derived B-cell differentiation factor also induces cytotoxic T lymphocytes.

Cells and mediators which participate in immunoglobulin synthesis by human mononuclear cells. III. Null cells secrete a factor(s) (human immunoglobulin synthesis/secretion-facilitating factor) that can replace the null cells in the synthesis of immunoglobulin by cultured B cells

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