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Increased secretion of hyperimmune antibodies following lipopolysaccharide stimulation of CD40‐activated human B cells in vitro
Author(s) -
Dumont Nellie,
Aubin Eric,
Proulx Dominic P.,
Lemieux Réal,
Bazin Renée
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02915.x
Subject(s) - cd40 , lipopolysaccharide , antibody , biology , secretion , cytokine , immune system , antigen , b cell , b 1 cell , polyclonal antibodies , naive b cell , immunology , microbiology and biotechnology , antigen presenting cell , in vitro , t cell , cytotoxic t cell , endocrinology , biochemistry
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.