Abstract
Macrophage migration inhibitory factor (MIF) is an upstream activator of innate immunity that regulates subsequent adaptive responses. It was previously shown that in macrophages, MIF binds to a complex of CD74 and CD44, resulting in initiation of a signaling pathway. In the current study, we investigated the role of MIF in B cell survival. We show that in B lymphocytes, MIF initiates a signaling cascade that involves Syk and Akt, leading to NF-kappaB activation, proliferation, and survival in a CD74- and CD44-dependent manner. Thus, MIF regulates the adaptive immune response by maintaining the mature B cell population.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Differentiation, B-Lymphocyte / chemistry
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Antigens, Differentiation, B-Lymphocyte / genetics
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Antigens, Differentiation, B-Lymphocyte / metabolism*
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B-Lymphocytes / cytology
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B-Lymphocytes / drug effects*
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B-Lymphocytes / immunology
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Base Sequence
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Cell Survival / drug effects
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DNA Primers / genetics
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Histocompatibility Antigens Class II / chemistry
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / metabolism*
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Hyaluronan Receptors / chemistry
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Hyaluronan Receptors / genetics
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Hyaluronan Receptors / metabolism*
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In Vitro Techniques
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Intramolecular Oxidoreductases / metabolism
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Intramolecular Oxidoreductases / pharmacology*
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Macrophage Migration-Inhibitory Factors / metabolism
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Macrophage Migration-Inhibitory Factors / pharmacology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Multiprotein Complexes
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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Signal Transduction / drug effects
Substances
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Antigens, Differentiation, B-Lymphocyte
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Cd44 protein, mouse
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DNA Primers
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Histocompatibility Antigens Class II
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Hyaluronan Receptors
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Macrophage Migration-Inhibitory Factors
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Multiprotein Complexes
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Recombinant Proteins
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invariant chain
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Intramolecular Oxidoreductases
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Mif protein, mouse