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.
Mättö
M
M
Department of Clinical Microbiology, Institute of Clinical Medicine, University of Kuopio, Kuopio, Finland. mikko.matto@uku.fi
Raunio
A-R
AR
Postila
V
V
Huttunen
K
K
Hirvonen
M-R
MR
Pelkonen
J
J
D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003432:Cross-Linking Reagents; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D008262:Macrophage Activation / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000955:Antigens, T-Independent; D003432:Cross-Linking Reagents; D007074:Immunoglobulin G; D020382:Interleukin-18; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma