Dysregulation of germinal centres in autoimmune disease

Nat Rev Immunol. 2009 Dec;9(12):845-57. doi: 10.1038/nri2637.


In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents--B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages--or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology*
  • B-Lymphocytes / immunology
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Humans
  • Lymphocyte Activation / immunology
  • T-Lymphocytes, Helper-Inducer / immunology