Augmented antibody response with premature germinal center regression in CD40L transgenic mice.
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.
Kishi
Yusuke
Y
Laboratory of Immunology, Graduate School of Biomedical Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Aiba
Yuichi
Y
Higuchi
Tetsuya
T
Furukawa
Koji
K
Tokuhisa
Takeshi
T
Takemori
Toshitada
T
Tsubata
Takeshi
T
D000276:Adjuvants, Immunologic / Q000235:genetics* / Q000502:physiology; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D023201:CD40 Ligand / Q000235:genetics* / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D006131:Growth Inhibitors / Q000235:genetics* / Q000502:physiology; D006241:Haptens / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates / Q000008:administration & dosage / Q000276:immunology; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D006241:Haptens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D023201:CD40 Ligand