Abstract
To define the role of TRAF proteins in CD40-dependent isotype switching in B cells, we introduced wild-type (WT) and mutant CD40 transgenes that lacked the binding motifs for TRAF6 (CD40deltaTRAF6), TRAF2 and TRAF3 (CD40deltaTRAF2/3), or both (CD40deltaTRAFs) into B cells of CD40(-/-) mice. The in vivo isotype switch defect in CD40(-/-) mice was fully corrected by WT and CD40deltaTRAF6, partially by CD40deltaTRAF2/3, and not at all by CD40deltaTRAFs transgenes. CD40-mediated isotype switching, proliferation, and activation of p38, JNK, and NFkappaB in B cells were normal in WT and CD40deltaTRAF6 mice, severely impaired in CD40deltaTRAF2/3, and absent in CD40deltaTRAFs mice. These results suggest that binding to TRAF2 and/or TRAF3 but not TRAF6 is essential for CD40 isotype switching and activation in B cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Motifs
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Animals
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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B-Lymphocytes / immunology
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CD40 Antigens / chemistry*
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CD40 Antigens / genetics
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CD40 Antigens / physiology
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Genetic Complementation Test
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Germinal Center / immunology
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Hemocyanins / immunology
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Immunoglobulin Class Switching / physiology*
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Immunoglobulins / biosynthesis
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Immunoglobulins / blood
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Lymphocyte Activation
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MAP Kinase Signaling System
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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NF-kappa B / physiology
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Protein Binding
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Protein Interaction Mapping
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Proteins / physiology*
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Recombinant Fusion Proteins / physiology
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Sequence Deletion
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Structure-Activity Relationship
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TNF Receptor-Associated Factor 2
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TNF Receptor-Associated Factor 3
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Up-Regulation
Substances
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Antigens, CD
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CD40 Antigens
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Immunoglobulins
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NF-kappa B
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Proteins
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Recombinant Fusion Proteins
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TNF Receptor-Associated Factor 2
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TNF Receptor-Associated Factor 3
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Hemocyanins
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keyhole-limpet hemocyanin