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Endothelial cells modulate both T-cell-dependent and T-cell-independent plaque-forming cell generation in vitro
J M Teitel1, A Shore, J McBarron
1Department of Medicine, St. Michael's Hospital, Canada.
Abstract:
The effects of live endothelial cells (EC), paraformaldehyde fixed EC, and EC supernatant were measured on pokeweed mitogen (PWM)-induced T-cell-dependent plaque-forming cell (PFC) generation by peripheral blood mononuclear cell (PBM). At low doses (less than or equal to 2 x 10(4) cells/culture) live EC helped PFC generation. At higher doses (greater than or equal to 10 x 10(4) cells/culture) the effect of live EC was always marked suppression (less than 10% of baseline PFC). In contrast both fixed EC and EC supernatant provided help exclusively over a wide dose range. The EC-helper effect enhanced the sensitivity of PBM to suboptimal PWM doses and also accelerated the rate of PFC generation during culture. EC influences on PFC could not be modified by gamma-interferon induction of surface DR which is known to modify EC accessory cell ability. There was also only minimal helper activity of live EC and fixed EC on the PFC generation by Epstein-Barr virus-induced cultures of purified B cells (which had been depleted of both T cells and monocytes). In contrast, suppression (greater than 97%) of PFC in isolated B-cell cultures was found even when EC constituted less than 1% of cultured cells. These results imply EC have the potential of providing multiple regulatory signals which modulate in vitro antibody production. EC-derived mechanisms are independent of their accessory cell function and require interaction with non-B cells for help, but suppression may occur directly at the B-cell level.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Live endothelial cells (EC) can either help or suppress antibody production by peripheral blood mononuclear cells (PBM), depending on their concentration. Fixed EC and EC supernatant consistently aid antibody generation.
Area of Science:
- Immunology
- Cell Biology
Background:
- Endothelial cells (EC) play a role in immune responses.
- The regulatory functions of EC in B-cell antibody production are not fully understood.
Purpose of the Study:
- To investigate the effects of live, fixed, and supernatant-derived endothelial cells (EC) on T-cell-dependent antibody production.
- To determine the dose-dependent effects of EC on plaque-forming cell (PFC) generation.
Main Methods:
- Peripheral blood mononuclear cells (PBM) were cultured with pokeweed mitogen (PWM) in the presence of varying doses of live EC, fixed EC, or EC supernatant.
- T-cell-dependent and Epstein-Barr virus-induced B-cell cultures were used to assess EC influence on PFC generation.
Main Results:
- Live EC exhibited dose-dependent effects, promoting PFC generation at low concentrations and suppressing it at high concentrations.
- Fixed EC and EC supernatant consistently provided help for PFC generation across a wide dose range.
- EC-mediated help enhanced PBM sensitivity to PWM and accelerated PFC generation.
- EC influence on PFC was independent of gamma-interferon-induced surface DR expression.
- EC-mediated suppression occurred directly at the B-cell level, while help required interaction with non-B cells.
Conclusions:
- Endothelial cells (EC) can exert dual regulatory roles in in vitro antibody production.
- EC-derived signals modulate antibody production through mechanisms distinct from accessory cell function.
- EC-mediated help requires non-B cell interaction, whereas suppression can directly impact B cells.