Human B cells and macrophages cooperate in T-cell-independent type 2 response

We have analysed separately the role of B-cell receptor (BCR) stimulation and the soluble second signal in the T-cell-independent type 2 (TI-2) B-cell response. We were able to show that human B cells and macrophages (Mphi) could function together in TI-type microbial response. Interestingly, BCR cross-linking of peripheral blood (PB) B cells enhanced IgG production induced by Mphi-derived growth factors whereas interleukin (IL)-12 + IL-18 had milder effect on IgG production. We demonstrated that B-cell-derived soluble mediators primed lipopolysaccharide (LPS)-stimulated Mphi for tumour necrosis factor-alpha (TNF-alpha) and IL-6 production significantly better than IFN-gamma, confirming the role of B cells in the activation of Mphi. We could show that human PB B cells were active cytokine producers and could be induced to produce interferon (IFN)-gamma mRNA in the presence of known Mphi cytokines, like IL-12 and IL-18. BCR stimulation also stabilized and enhanced the IFN-gamma mRNA production induced by IL-12 and IL-18. In addition, our novel finding was that a known Mphi cytokine, IL-10, induced the expression of IFN-gamma mRNA from human B-cell line (HF28R0) cells. In summary, we propose a model for the active role of B cells in the induction of the inflammatory response during TI antigen challenge in close collaboration with Mphi.