Abstract
Although CD40 signaling is required for activation and differentiation of B cells, including germinal center (GC) formation and generation of memory B cells, in vivo generation of CD40 signaling augments plasma cell differentiation but disrupts GCs. Thus, CD40 signaling is thought to direct B cells to extrafollicular plasma cell fate rather than GC formation. In this study, we analyzed CD40L transgenic (CD40LTg) mice that constitutively express CD40L on B cells. After immunization, activation of B cells, but not dendritic cells, was augmented, although dendritic cells can be activated by CD40 ligation. Bone marrow chimera carrying CD40LTg and nontransgenic B cells showed increased Ab production from transgenic, but not from coexisting nontransgenic, B cells, suggesting that CD40L on a B cell preferentially stimulates the same B cell through an autocrine pathway, thereby augmenting Ab production. Although GCs rapidly regressed after day 5 of immunization and failed to generate late-appearing high-affinity Ab, CD40LTg mice showed normal GC formation up to day 5, as well as normal generation of long-lived plasma cells and memory B cell responses. This observation suggests that CD40 signaling does not block GC formation or differentiation of GC B cells, but it inhibits sustained expansion of GC B cells and augments B cell differentiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / genetics*
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Adjuvants, Immunologic / physiology
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Animals
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism
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B-Lymphocyte Subsets / pathology
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CD40 Ligand / genetics*
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CD40 Ligand / physiology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cells, Cultured
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Female
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Germinal Center / cytology
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Germinal Center / immunology*
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Germinal Center / metabolism
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Growth Inhibitors / genetics*
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Growth Inhibitors / physiology
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Haptens / administration & dosage
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Haptens / immunology
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Immunoglobulin G / biosynthesis*
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Immunoglobulin M / biosynthesis*
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Male
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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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Mice, Transgenic
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Molecular Sequence Data
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Nitrophenols / administration & dosage
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Nitrophenols / immunology
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Phenylacetates / administration & dosage
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Phenylacetates / immunology
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Growth Inhibitors
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Haptens
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Immunoglobulin G
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Immunoglobulin M
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Nitrophenols
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Phenylacetates
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4-hydroxy-5-nitrophenyl acetic acid
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CD40 Ligand
Associated data
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GENBANK/AB062567
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GENBANK/AB062568
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GENBANK/AB062569
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GENBANK/AB062570
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GENBANK/AB062571
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GENBANK/AB062572
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GENBANK/AB062573
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GENBANK/AB062574
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GENBANK/AB062575
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GENBANK/AB062576
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GENBANK/AB062577
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GENBANK/AB062578
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GENBANK/AB062579
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GENBANK/AB062580
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GENBANK/AB062581
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GENBANK/AB062582
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GENBANK/AB062583
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GENBANK/AB062584
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GENBANK/AB062585
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GENBANK/AB062586
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GENBANK/AB062587
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GENBANK/AB062588
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GENBANK/AB062589
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GENBANK/AB062590
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GENBANK/AB062591
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GENBANK/AB062592
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GENBANK/AB062593