The generation of thymus-independent germinal centers depends on CD40 but not on CD154, the T cell-derived CD40-ligand.
In this report, we show that the formation of germinal center (GC)-like structures to thymus-independent type 2 antigens in mice depends on intact signals through CD40, but does not depend on T cell-derived CD40-ligand (CD154). In addition, we show that follicular dendritic cells (FDC) are also critical to thymus-independent GC formation, as their depletion by blockade of lymphotoxin-beta receptor signals abrogated GC development unless the responding B cells bound antigen with high affinity. Further evidence that immune complexes drove this CD40-dependent B cell proliferation was provided by the observation that an antibody that detects immune complexes containing complement component 4 on FDC also inhibited thymus-independent GC formation when injected in vivo at the time of immunization. Finally, we show that thymus-independent B cell proliferation was associated with class switching to IgG3, as IgG3(+) antigen-specific switched B cells could be visualized directly in GC, suggesting that immune complexes can provide the signals for class switching within GC in the absence of CD154.
Gaspal
Fabrina M C
FM
MRC Centre for Immune Regulation, University of Birmingham, Birmingham, UK.
McConnell
Fiona M
FM
Kim
Mi-Yeon
MY
Gray
David
D
Kosco-Vilbois
Marie H
MH
Raykundalia
Chandra R
CR
Botto
Marina
M
Lane
Peter J L
PJ
D000818:Animals; D000955:Antigens, T-Independent / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics / Q000502:physiology*; D005260:Female; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism*; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000955:Antigens, T-Independent; D019013:CD40 Antigens; D007074:Immunoglobulin G; D023201:CD40 Ligand