Abstract
NK cells are an important component of the innate immune system that can also interact with B cells in a mutually productive manner. We have previously shown that activated B cells can induce NK cells to up-regulate their secretion of IFN-gamma. In this study, we show that B cells, and, particularly, marginal zone B cells, can, in addition, induce NK cells via direct cell-cell interactions to express mRNA encoding the Th2 cytokine IL-13. The induction of NK cell IL-13 mRNA expression requires the ligation of the CD244 receptor by the CD48 ligand on B cells via signaling pathways that depend upon expression of the X-linked lymphoproliferative disease gene product, SH2D1A/DSHP/SAP (SLAM-associated protein, or SAP) in NK cells. Thus, the positive signals attributed to the B cell activation of CD244 on murine NK cells appears to be more similar to the activity of CD244 on human cells. The induction of IL-13 mRNA by B cells may account for the effect of NK cells on the generation of Th2-type responses in the presence of some adjuvants.
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / physiology*
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Cell Communication / genetics
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Cell Communication / immunology
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Cells, Cultured
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Coculture Techniques
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / deficiency
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Interferon-gamma / genetics
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Interleukin-13 / biosynthesis*
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Interleukin-13 / genetics
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Interleukin-13 / physiology
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Intracellular Signaling Peptides and Proteins / deficiency
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / physiology*
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism*
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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RNA, Messenger / biosynthesis
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Receptors, Cell Surface / physiology
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Receptors, Immunologic / deficiency
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Receptors, Immunologic / genetics
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Receptors, Immunologic / physiology*
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Signaling Lymphocytic Activation Molecule Associated Protein
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Signaling Lymphocytic Activation Molecule Family
Substances
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Antigens, CD
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CD244 protein, human
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Cd244a protein, mouse
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Interleukin-13
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Intracellular Signaling Peptides and Proteins
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Membrane Glycoproteins
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Immunologic
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SH2D1A protein, human
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Sh2d1a protein, mouse
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Signaling Lymphocytic Activation Molecule Associated Protein
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Signaling Lymphocytic Activation Molecule Family
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Interferon-gamma