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Biomedical subjects

E Severinson

Publications and source records attributed to E Severinson.

43 records · Page 3Linked to original sources
PubMed1983

Activation of BCL1 cells by polyclonal activators and inhibition of growth and IgM secretion by anti-IgM.

Bacterial lipoprotein (LP) and lipopolysaccharide (LPS) both activated an in vitro line of the B-cell tumour BCL1 to IgM secretion, as determined by the protein A plaque assay. LPS but not LP activation was inhibited by polymyxin B. Activation with both LPS and LP resulted in a less than additive response. Several clones of BCL1 were tested, and all responded to both LPS and LP. Both LPS and LP induced broad dose-response curves in normal lymphocytes, recently cloned BCL1 cells, and cloned and synchronized (G1 phase) BCL1 cells. This suggests that the dose-response curve cannot be due to accumulation of responding cells with different threshold sensitivities for activation. We cannot exclude the possibility that the broad dose-response curve is due to a heterogeneity of the LPS or LP preparation. The results indicate that LPS and LP induce similar signals in BCL1 cells. Furthermore, binding to the cell membrane and activation of BCL1 cells by LPS or LP seem to be separate events. An anti-IgM antiserum inhibited spontaneous DNA synthesis and spontaneous and LP-induced IgM secretion of BCL1 cells. Equal inhibition was observed with F(ab')2 fragments but not with Fab fragments of the antiserum, suggesting that cross-linking of IgM bound to the cell surface membrane-induced inhibition. Supernatants from concanavalin A (Con A)-activated spleen cells induced BCL1 cells to secrete IgM. Fab anti-IgM added alone to BCL1 cells did not induce IgM secretion. Furthermore, Fab anti-IgM plus Con A supernatant did not induce a higher response than the supernatant alone. This suggests that inductive signals via the IgM receptor do not occur in BCL1 cells.

Animals↗
PubMed1983

The polyclonal lipopolysaccharide response is accessory-cell-dependent.

Different concentrations of spleen cells from C57BL.10 mice were activated with lipopolysaccharide (LPS), and DNA synthesis and IgM and IgG secretion were measured. The dilution curve was sigmoid, and the response was rapidly lost below a certain cell concentration. In the presence of thymocytes or spleen cells from the LPS-non-responder strain C57BL.10/ScCr the dilution curve for the LPS response of cells from C57BL.10 mice became linear, and the overall response was increased. Irradiated cells could not restore the response at suboptimal cell concentrations. In addition, enriched T cells restored the response as well as normal spleen cells, whereas enriched B cells did not. We compared the restoring capacity of different filler cells for the LPS response with that of a plasmacytoma cell line cultured at suboptimal cell concentrations. The results are compatible with the idea that the filler cells provide growth-stimulating activity to LPS-responsive cells but growth-supporting activity to the tumour cells. Furthermore, highly enriched B-cell populations respond poorly to LPS, but the response can be partly restored by filler cells. These data suggest that the LPS response is accessory-cell-dependent.

Animals↗
PubMed1982

Limited life span of extensively proliferating B cells: no evidence for a continuous class or subclass switch.

The polyclonal B cell activators (PBA) dextran sulphate (DxS) and lipopolysaccharide (LPS) induce a marked synergistic response in mouse splenic B cells. Such activated B cell blasts could be maintained in culture for a total period of 15 to 20 days, provided the cells were subcultured repeatedly in fresh medium containing the PBA. After this time period activation could no longer be achieved. The B cell blasts responded at all times better to LPS plus DxS than to either PBA added alone. Furthermore, LPS-induced B cell blasts also responded better to LPS plus DxS than to LPS alone. Activated cells secreted IgM and switched to IgG3 and IgG2b secretion. At the end of the culture period, approximately one cell out of four secreted IgG. The kinetics of IgG3 and IgG2b production were similar, and the fraction of cells secreting these subclasses increased at similar rates throughout the culture period. We conclude that high-rate secreting and proliferating B cells have a limited life span. Furthermore, most activated B cells do not seem to go through a continuous subclass switch but keep on secreting the subclass they originally switched to.

Animals↗
PubMed1981

A synergistic polyclonal response to dextran sulphate and lipopolysaccharide: immunoglobulin secretion and cell requirements.

The effects of the simultaneous addition of lipopolysaccharide (LPS) and dextran sulphate (DxS) were studied in a low-cell density culture system, which enables extensive cell proliferation and high immunoglobulin secretion. Using these two mitogens, a synergistic response was observed, with regard to both cell division and IgM secretion. However, only a very low IgG production could be detected. This was caused by the extensive cell proliferation, leading to suboptimal culture conditions. Thus, when the blasts were recultured at a lower density or when a lower initial cell concentration was used, a high IgG response was obtained. The synergistic response induced by LPS plus DxS was independent of T cells. Furthermore, no apparent need for phagocytic cells was found. Both the LPS- and the LPS plus DxS-induced activation led to a switch, preferentially to IgG2b and IgG3 secretion. This subclass pattern was not changed when the cultures were lacking functional T cells.

Animals↗
PubMedDate not supplied

Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter.

Complementary DNA encoding the IgG1 induction factor, the first lymphokine directed to B lymphocytes, from a murine T-cell line has been cloned using a new strategy. The putative primary amino-acid sequence was deduced from the nucleotide sequence determined. The lymphokine synthesized by the direction of this cloned cDNA has many other functions, such as production of B-cell growth factor-1 and induction of Ia on B cells.

Amino Acid Sequence↗
PubMedDate not supplied

Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II.

Proliferation and maturation of antigen-stimulated B cells are regulated by several soluble factors derived from macrophages and T cells. These soluble factors are functionally divided into two groups: B-cell growth factor (BCGF), thought to be involved in B-cell proliferation; and B-cell differentiation factor (BCDF), responsible for maturation of activated B cells into immunoglobulin-secreting cells. This classification needs to be re-examined in the light of the recent cloning of complementary DNA encoding IgG1 induction factor (interleukin-4, IL-4) from the 2.19 mouse T-cell line. Recombinant IL-4 has BCGF and BCDF activities and affects B cells, T cells and mast cells (refs 7, 8; our unpublished data). Another well-characterized B-cell factor is T-cell replacing factor (TRF), which, when secreted by the murine T-cell hybridoma B151K12, is defined by two activities: induction of IgM secretion by BCL1 leukaemic B-cell line; and induction of secondary anti-dinitrophenol (DNP) immunoglobulin G (IgG) synthesis in vitro by DNP-prime B cells. Although TRF from B151K12 was classified as BCDF, purified TRF has BCGF-II activity. To elucidate the molecular properties of TRF we isolated cDNA encoding TRF from the 2.19 T-cell line and report here the structure and multiple activities of this lymphokine.

Animals↗