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

Dysregulation of germinal centres in autoimmune disease.

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John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT 2601, Australia.


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.

[Indexed for MEDLINE]

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