The generation of thymus‐independent germinal centers depends on CD40 but not on CD154, the T cell‐derived CD40‐ligand

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Abstract
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‐β 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.