T cell-dependent activation of resting B cells: requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors.

Anderson, James; Melchers, Fritz

doi:10.1073/pnas.78.4.2497

Cited by 104 publications

(40 citation statements)

References 21 publications

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“…Fourth, it has been demonstrated (14) that clonal expansion and differentiation of individual hapten-specific B cells require soluble factors distinct from IL-2. Fifth, many investigators have successfully separated IL-2 by biochemical procedures from BCGF and BCDF in the murine system (38,39) as well as in the human system (11)(12)(13)35).…”

Section: Discussionmentioning

confidence: 99%

Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function.

Muraguchi¹,

Kehrl²,

Longo³

et al. 1985

The Journal of Experimental Medicine

220

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It has been demonstrated (1, 2) that a number of antigen-nonspecific soluble factors exist that can transmit signals for growth and/or differentiation among lymphoid cells, particularly T lymphocytes, and may play a major role in the regulation of the immune response. Recent studies (3-5) in both murine and human systems have revealed that such antigen-nonspecific soluble factors also play a critical role in regulating the proliferation and differentiation of B iymphocytes.We have attempted to delineate the minimal and optimal signals required for the induction of resting human B cells to proliferate as well as the signals required for the induction of activated B cells to differentiate into immunoglobulinsecreting cells (4,5). In this regard~ we have recently demonstrated (6-8) that Staphylococcus aureus Cowan I (SAC) 1 or a high concentration of antiimmunoglobulin antibody that interacts with the B cell surface immunoglobulin (slg) directly induces the proliferation of resting human B cells, while a less powerful slg-mediated signal, such as that delivered by low concentrations of anti-Ig antibody, results in the activation of B cells without subsequent proliferation. These activated B cells, presumably arrested in the G1 phase of the B cell cycle, were able to respond to exogeneous T cell-derived B cell growth factor (BCGF), now designated B cell stimulatory factor (BSF) (9), to enter the S phase of the cell cycle. These activated B cells can in turn be induced to differentiate into Igsecreting cells by B cell differentiation factors (BCDF), originally referred to as T cell-replacing factors (10). These BCDF have been shown to be biochemically separable from interleukin 2 (IL-2) and BSF (11-13).It is currently controversial whether IL-2 exerts a direct effect on B cell function. Certain reports (3, 14) state that it is unlikely that IL-2 directly affects B cells; however, other studies indicate that IL-2 has an important role in the J Abbrevmtions used in this paper:

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Section: Discussionmentioning

confidence: 99%

Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function.

Muraguchi¹,

Kehrl²,

Longo³

et al. 1985

The Journal of Experimental Medicine

220

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“…It has been clearly demonstrated that T lymphocytes produce lymphokines that cause activated B lymphocytes to proliferate: this factor has been termed B cell growth factor (BCGF)' (1). Furthermore, distinct lymphokines act on the proliferating B cells to induce them to differentiate (2).…”

Section: Introductionmentioning

confidence: 99%

Human B lymphoma cell line producing B cell growth factor.

Ambrus¹,

Fauci²

1985

J. Clin. Invest.

103

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Namalva, a human B cell lymphoma line, produced a factor with a molecular weight of -60,000 which enhanced the proliferation of normal activated human B lymphocytes. The factor also enhanced the proliferation of certain B cell lines. It can be distinguished physiologically and biochemically from other lymphokines known to enhance B cell proliferation, namely, interleukin (IL) 1, IL 2, and interferon. The production of B cell growth factor by B cell tumor lines may contribute to their ability to grow autonomously and may reflect an important component of the neoplastic potential of the cell. B cell growth factor produced by tumors may also affect normal cells in vivo.

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“…Additionally, male BXSB early-life SLE can be transferred with anti-Thy-l.2 + complement (C) treated male bone marrow cells given to thymectomized, lethally irradiated female BXSB recipients. 2 It is now clear that normal B cells require several signals to become activated, to proliferate, and to undergo differentiation to antibody-producing ceils (16,21). In this study we have used in vitro assays for which two or more identifiable signals are necessary to obtain B cell responses and compared lupus mice versus normal control mice in regard to: (a) the number of signals required for activation and differentiation and (b) the magnitude of responsiveness to these signals.…”

mentioning

confidence: 99%

B cell dependence on and response to accessory signals in murine lupus strains.

Prud’homme¹,

Balderas²,

Dixon³

et al. 1983

The Journal of Experimental Medicine

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B cell hyperactivity, a feature common to all lupus-prone murine strains, may be caused by hyperresponsiveness to, overproduction of, or bypassing of certain signals required for B cell activation, proliferation, and differentiation. In this study, we have compared the responses of B cells from three lupus-prone strains of mice (BXSB males, MRL and NZB/W females) and normal strains in a number of assays for which two or more signals are required to obtain a response. In medium to low density cultures of B cells from BXSB and NZB/W but not MRL/l lupus mice, the cells' proliferation induced by bacterial lipopolysaccharide (LPS) or anti-mu antibody was much higher than that of B cells from normal controls. At low B cell density, polyclonal activation by these substances and subsequent Ig secretion were dependent on accessory signals present in supernatants of concanavalin A-treated normal lymphocytes (CAS) or on the MRL/l proliferating T cell-derived B cell differentiation factor (L-BCDF) in both lupus-prone and immunologically normal mice. However, the responses of B cells from BXSB and NZB/W, but not MRL/l, mice to these accessory signals were higher than those of normal mice. Ig synthesis by fresh B cells of BXSB and NZB/W mice cultured in the absence of mitogens but in the presence of CAS or L-BCDF was higher than by similar cells from other strains, suggesting an increased frequency of B cells activated in vivo in these two autoimmune strains of mice. The patterns of IgG subclass secretion in response to LPS (without added CAS or L-BCDF) were abnormal in all lupus strains, with a predominance of IgG2b and/or IgG2a and low levels of IgG3, contrary to normal B cells for which IgG3 synthesis predominated. However, IgG1 synthesis in vitro by autoimmune and normal B cells alike was highly dependent on T cell-derived soluble mediators. Antigen-specific responses to SRBC in vitro of B cells from all lupus strains, like those of B cells from normal strains, required a minimum of three signals (antigen, LPS, T cell-derived antigen nonspecific helper factors). Yet, once triggered, B cells of BXSB and NZB/W mice gave higher responses than those of the other strains. We conclude that B cells of lupus mice have signal requirements similar to those of normal mice. Nevertheless, B cells of BXSB and NZB/W, but not MRL/l, lupus mice hyperrespond or process some accessory signals abnormally.

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T cell-dependent activation of resting B cells: requirement for both nonspecific unrestricted and antigen-specific Ia-restricted soluble factors.

Cited by 104 publications

References 21 publications

Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function.

Interleukin 2 receptors on human B cells. Implications for the role of interleukin 2 in human B cell function.

Human B lymphoma cell line producing B cell growth factor.

B cell dependence on and response to accessory signals in murine lupus strains.

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