AID and caspase 8 shape the germinal center response through apoptosis

J Immunol. 2013 Dec 15;191(12):5840-7. doi: 10.4049/jimmunol.1301776. Epub 2013 Nov 15.

Abstract

Germinal centers (GCs) are clusters of activated B cells that form in secondary lymphoid organs during a T-dependent immune response. B cells enter GCs and become rapidly proliferating centroblasts that express the enzyme activation-induced deaminase (AID) to undergo somatic hypermutation and class-switch recombination. Centroblasts then mature into centrocytes to undergo clonal selection. Within the GC, the highest affinity B cell clones are selected to mature into memory or plasma cells while lower affinity clones undergo apoptosis. We reported previously that murine Aicda(-/-) GC B cells have enhanced viability and accumulate in GCs. We now show that murine Aicda(-/-) GC B cells accumulate as centrocytes and inefficiently generate plasma cells. The reduced rate of plasma cell formation was not due to an absence of AID-induced DNA lesions. In addition, we show that the deletion of caspase 8 specifically in murine GC-B cells results in larger GCs and a delay in affinity maturation, demonstrating the importance of apoptosis in GC homeostasis and clonal selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens / immunology
  • Apoptosis / physiology*
  • Autoimmune Lymphoproliferative Syndrome / immunology*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / pathology
  • Caspase 8 / genetics
  • Caspase 8 / physiology*
  • Cell Division
  • Clonal Selection, Antigen-Mediated*
  • Cytidine Deaminase / deficiency
  • Cytidine Deaminase / genetics
  • Cytidine Deaminase / physiology*
  • DNA Breaks, Double-Stranded
  • Germinal Center / immunology*
  • Germinal Center / pathology
  • Immunization
  • Immunoglobulin Class Switching
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / pathology*
  • Mice
  • Mice, Congenic
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasma Cells / pathology
  • Radiation Chimera
  • Receptors, Antigen, B-Cell / immunology
  • Somatic Hypermutation, Immunoglobulin

Substances

  • Antigens
  • Receptors, Antigen, B-Cell
  • Casp8 protein, mouse
  • Caspase 8
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase