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

Eur J Immunol. 2006 Jul;36(7):1665-73. doi: 10.1002/eji.200535339.

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-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.

MeSH terms

  • Animals
  • Antigens, T-Independent / immunology*
  • CD40 Antigens / genetics
  • CD40 Antigens / physiology*
  • CD40 Ligand / genetics
  • CD40 Ligand / physiology*
  • Female
  • Germinal Center / immunology*
  • Germinal Center / metabolism*
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulin G / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism

Substances

  • Antigens, T-Independent
  • CD40 Antigens
  • Immunoglobulin G
  • CD40 Ligand