Requirement for macrophages or for macrophage‐ or T cell‐derived factors in the mitogenic stimulation of murine B lymphocytes by lipopolysaccharides

Corbel, C.; Melchers, Fritz

doi:10.1002/eji.1830130703

Cited by 86 publications

(27 citation statements)

References 62 publications

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“…2). These results confirm earlier observations (10) showing that neither a factors, nor p factors, nor immunoglobulin-specific antibodies alone are sufficient for initiation and completion of the next cell cycle after mitosis.…”

supporting

confidence: 92%

Three restriction points in the cell cycle of activated murine B lymphocytes.

Melchers¹,

Lernhardt²

1985

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

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The cell cycle of activated B lymphocytes was found to be controlled by three restriction points. The first occurs immediately after mitosis and was found to be controlled by the binding of Sepharose-bound, immunoglobulin-specific antibodies to surface membrane-bound immunoglobulin. Exposure to this stimulus as short as 15 min or as long as 36 hr allowed B cells to move into the G1 phase up to the next restriction point. The second restriction point was observed to be =4 hr after mitosis, in the G, phase of the cycle and 3-4 hr before the B cells entered S phase, and was found to be controlled by a-type B-cell growth factors produced by the P388D1 macrophage line. A third restriction point occurs in the G2 phase, 2-4 hr before mitosis, and is apparently controlled by ,8-type B-cell growth factors that are likely to be produced by helper T lymphocytes.DNA replication and mitosis in B lymphocytes are under the control (i) of antigen that binds to variable regions of surface membrane-bound immunoglobulin molecules and (ii) of two types of B-cell growth factors, a and P3, which are produced by macrophages (accessory cells) and by helper T lymphocytes, respectively (for reviews, see refs. 1 and 2). B cells have to be excited from their resting, Go state of the cell cycle to become susceptible to the action of a and 13 factors. This can be achieved in antigen-specific, major histocompatibility complex (MHC)-restricted, T-cell-dependent ways, as well as in polyclonal, MHC-unrestricted, T-cell-independent ways. For the experiments reported in this paper, we activated murine B lymphocytes polyclonally with the mitogen lipopolysaccharide (LPS; ref. 3). The activated B lymphocytes then were synchronized by size-selection using velocity sedimentation (4). This allowed us to investigate in serumsubstituted cultures (5, 6) the roles of ,u heavy chain-specific monoclonal antibodies (7), as agents acting via surface-bound IgM on B lymphocytes, and of the two types of B-cell growth factors in the control of the cell cycle of these activated B cells. The three interactions-with Ig-specific antibodies, a factors, and /3 factors-define three restriction points in the B-cell cycle. MATERIALS AND METHODSMice, Cells, and Culture Conditions. Spleen cells from 6-to 12-week-old C57BL/6J nu/nu mice (obtained from the Institut fur Biologisch-Medizinische Forschung A.G., Fullinsdorf, Switzerland) were prepared and enriched for small, resting cells by velocity sedimentation at unit gravity (4) as described (8). They were cultured at 5 x 105 cells per ml in serum-substituted medium (6) (Pharmacia, Uppsala, Sweden) at 2.5 mg of Aki5 protein per ml of swollen Sepharose beads. After saturation of the uncoupled active groups on the Sepharose (done as recommended by the manufacturer), the washed beads were kept as a 10% (vol/vol) suspension in either sterile 0.9% NaCl or sterile culture medium. They were used as a final 1% suspension in all experiments described in Results. To remove the beads coated with immunoglobulin-specific antibodie...

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supporting

confidence: 92%

Three restriction points in the cell cycle of activated murine B lymphocytes.

Melchers¹,

Lernhardt²

1985

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

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“…11 Earlier in vitro studies suggested that the TI B-cell response in mice to TNP-haptenated antigens such as TNP-Ficoll, TNPlipoprotein (LP), and TNP-Brucella abortus directly required macrophages. [12][13][14][15] Interestingly, interleukin 1 (IL-1) appeared to substitute for the requirement of macrophages in B-cell responses to TI antigens. In addition, IL-1-secreting cells reconstitute the response of macrophage-depleted splenic cells to TI antigens.…”

Section: Introductionmentioning

confidence: 99%

Macrophage- and dendritic cell—dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF

Craxton

Magaletti

Ryan

et al. 2003

Blood

291

233

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“…Macrophages, as a source of costimulatory signals, are essential for the generation of robust proliferation of B and T cells (7). It is therefore not surprising that they appear to be primary targets for factors modulating lymphocyte function.…”

Section: Discussionmentioning

confidence: 99%

“…The prevailing evidence supports a significant role for accessory cells in the activation of T and B cells both in vivo and in vitro (7,41). This has prompted numerous investigations into the role of macrophages in helminth-mediated immunomodulation of lymphocyte function (2,15,17,22,27,28,36).…”

mentioning

confidence: 99%

Modulation of B-Cell Proliferative Response by a Soluble Extract ofNippostrongylus brasiliensis

2000

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We and others have previously shown that nematodes or nematode products can stimulate or inhibit the generation of lymphocyte responses, suggesting that nematodes exert diverse effects on the developing immune responses of their host. In this study we examined the immunomodulatory effect of a soluble extract of Nippostrongylus brasiliensis (adult worm homogenate [AWH]) on B-cell responsiveness. We found that the extract inhibited the proliferation of B cells to lipopolysaccharide (LPS) stimulation in a dose-dependent manner. This effect was specific to B cells, since the extract did not inhibit T-cell proliferation to concanavalin A or anti-CD3 stimulation. The data presented here confirm that the extract is not toxic to B cells. We present evidence that the active factor is proteinaceous in nature and that the inhibitory activity is restricted to the adult stage of Nb. The extract does not appear to interfere with early activation events since it can be added up to 48 h after LPS stimulation, and it inhibited responses to phorbol myristate acetate and ionomycin. Furthermore, the proliferation of B cells to other activators was also inhibited by AWH. This observation shows that the inhibitory activity of AWH is not restricted to LPS-mediated B-cell proliferation. We present evidence that, in the absence of accessory cells, the inhibitory effect of the extract was ablated. This observation shows that the activity of AWH is not mediated directly on B cells but is mediated via the production of negative signals from accessory cells (macrophages), which affect a downstream pathway required by all B-cell activators tested. These effects on B-cell and accessory cell function are likely to have a significant effect on the outcome of infections experienced concurrently.To ensure survival and continuation of their life cycle, nematodes have evolved a unique relationship with their hosts. Part of this accommodation is the ability to modulate host immune responsiveness (25). Modulation of lymphocyte function has been widely reported among nematodes (2,3,19,21,22,28) and other parasites (6,15,27,36). For example, we have previously shown a dramatic potentiation of antibody responses to third party antigens by treatment with a body fluid extract of Ascaris suum (19). This observation is significant in that it suggests that the modulatory effect of nematodes on immune responses is far-reaching and may have profound effects on developing immune responses to unrelated antigenic challenge. We have also reported the presence of a B cell mitogen in the body fluid of A. suum, which stimulated G 0 B cells to enter the cell cycle (20). This activity of the Ascaris factor was dependent on viable accessory cells.The effect of helminth products on the developing immune response is likely to be complex. For example, in contrast to the immunostimulatory activity of the body fluid of Ascaris reported above, Ferreira and coworkers (13) and Soares and coworkers (39, 40) have reported immunomodulatory factors in secretions of A. suum, which a...

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Requirement for macrophages or for macrophage‐ or T cell‐derived factors in the mitogenic stimulation of murine B lymphocytes by lipopolysaccharides

Cited by 86 publications

References 62 publications

Three restriction points in the cell cycle of activated murine B lymphocytes.

Three restriction points in the cell cycle of activated murine B lymphocytes.

Macrophage- and dendritic cell—dependent regulation of human B-cell proliferation requires the TNF family ligand BAFF

Modulation of B-Cell Proliferative Response by a Soluble Extract ofNippostrongylus brasiliensis

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