Lymph node germinal centers form in the absence of follicular dendritic cell networks.
Follicular dendritic cell networks are said to be pivotal to both the formation of germinal centers (GCs) and their functions in generating antigen-specific antibody affinity maturation and B cell memory. We report that lymphotoxin beta-deficient mice form GC cell clusters in the gross anatomical location expected of GCs, despite the complete absence of follicular dendritic cell networks. Furthermore, antigen-specific GC generation was at first relatively normal, but these GCs then rapidly regressed and GC-phase antibody affinity maturation was reduced. Lymphotoxin beta-deficient mice also showed substantial B cell memory in their mesenteric lymph nodes. This memory antibody response was of relatively low affinity for antigen at week 4 after challenge, but by week 10 after challenge was comparable to wild-type, indicating that affinity maturation had failed in the GC phase but developed later.
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
P A
PA
Koni
R A
RA
Flavell
D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007156:Immunologic Memory; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation; D008233:Lymphotoxin-alpha / Q000235:genetics*; D053308:Lymphotoxin-beta; D008565:Membrane Proteins / Q000235:genetics*; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation
C505887:Ltb protein, mouse; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins