Dysregulation of germinal centres in autoimmune disease.
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.
Vinuesa
Carola G
CG
John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT 2601, Australia. carola.vinuesa@anu.edu.au
Sanz
Iñaki
I
Cook
Matthew C
MC
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology