engleski

Th1-polarized cytokine production by human B cells

B cells, in their resting state, lack antigen presenting capacity, but shortly after crosslinking of BCR and/or ligation of CD40, they upregulate B7 molecules and differentiate into efficient APC. The recent finding that murine na&iuml ; ve B cells can differentiate into effector subsets 1 and 2, which produce Th1- and Th2-polarising cytokines, respectively, has suggested that B cells have the capacity to amplify or maintain an ongoing polarised immune response. However, the activation requirements of naive vs memory B cells for cytokine production could be different. Human na&iuml ; ve and memory B cells can be readily distinguished by the expression of CD27, a molecule that is absent on na&iuml ; ve B cells. Here we compared human na&iuml ; ve (IgM+IgD+CD27-CD38-IgG-IgA-) and memory (IgM-IgD-CD27+CD38-IgG+/-IgA+/-) tonsillar B cells for their expression of IL-12 and IL-23 and the signals that induce these cytokines. We found that B cell subsets when engaged in signaling via BCR and CD40 do not modulate p35 subunit of IL-12 as measured by quantitative PCR. CD40 ligation induced p40 IL-12 measured both by quantitative PCR and p40 ELISA significantly more in memory B cells. However, neither B cell subsets secreted significant amounts of p70 IL-12. Memory B cells also expressed more p19 IL-23 mRNA, but the major signal responsible for upregulation of this cytokine was BCR trigerring. The inability of B cells to produce the p70 IL-12 heterodimer would limit their capacity as frontline APC for the initiation of Th1 responses. However, the ability of memory B cells to produce IL-23 offers this B cell subset the capacity to maintain and amplify Th1-direction of skewing following subsequent encounters with the antigen.

B cells

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