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Immunity. 2012 Aug 24;37(2):199-207. doi: 10.1016/j.immuni.2012.08.002.

Regulation of humoral immunity by complement.

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Immune Disease Institute and Program in Molecular and Cellular Medicine, Children's Hospital and Department of Pediatrics, Harvard Medical School, Boston, 02115 MA, USA.


The complement system of innate immunity is important in regulating humoral immunity largely through the complement receptor CR2, which forms a coreceptor on B cells during antigen-induced activation. However, CR2 also retains antigens on follicular dendritic cells (FDCs). Display of antigen on FDCs is critical for clonal selection and affinity maturation of activated B cells. This review will discuss the role of complement in adaptive immunity in general with a focus on the interplay between CR2-associated antigen on B cells with CR2 expressed on FDCs. This latter interaction provides an opportunity for memory B cells to sample antigen over prolonged periods. The cocrystal structure of CR2 with its ligand C3d provides insight into how the complement system regulates access of antigen by B cells with implications for therapeutic manipulations to modulate aberrant B cell responses in the case of autoimmunity.

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