Free Content Increased secretion of hyperimmune antibodies following lipopolysaccharide stimulation of CD40-activated human B cells in vitro

Authors: Dumont, Nellie; Aubin, Eric; Proulx, Dominic P.; Lemieux, Réal; Bazin, Renée

Source: Immunology, Volume 126, Number 4, April 2009 , pp. 588-595(8)

Publisher: Wiley-Blackwell

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Abstract:

Summary

Human B cells can be cultured ex vivo for a few weeks, following stimulation of the CD40 cell surface molecule in the presence of recombinant cytokines such as interleukin-4 (IL-4). However, attempts to produce polyclonal antigen-specific human antibodies by in vitro culture of human B cells obtained from immunized donors have not been successful. It has been shown in mice that lipopolysaccharide (LPS) is a potent mitogen for B cells and plays an important role in the generation of antigen-specific antibody responses. Although it has long been believed that LPS has no direct effect on human B cells, recent data indicating that IL-4-activated human B cells are induced to express Toll-like receptor-4, the main LPS receptor, prompted us to study the effects of LPS on the proliferation and antibody secretion of human B cells. Our results showed that LPS caused a reduction in the expansion of CD40-activated human B cells, accompanied by an increase in antigen-specific antibody secretion. This result suggested that some, but not all, B cells were able to differentiate into antibody-secreting cells in response to LPS. This increased differentiation could be explained by the observation that LPS-stimulated human B cells were induced to secrete higher amounts of IL-6, a pleiotropic cytokine well-known for its B-cell differentiation activity. In vivo, the effect of LPS on cytokine secretion by B cells may not only enhance B-cell differentiation but also help to sustain a local ongoing immune response to invading Gram-negative bacteria, until all pathogens have been cleared from the organism.

Keywords: antibody secretion; human B cell; interleukin-6; lipopolysaccharide

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2567.2008.02915.x

Publication date: 2009-04-01

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