SCIENCE SIGNALING

Receptor Rendezvous

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Science  27 Jun 2008:
Vol. 320, Issue 5884, pp. 1697
DOI: 10.1126/science.320.5884.1697c

B cell systems that protect organisms from viral infection walk a fine line because the molecules they detect—such as unmethylated DNA—can be derived from the host, and an overzealous defense results in autoimmune disease. Chaturvedi et al. describe how components of the adaptive and innate immune systems—B cell receptors (BCRs) and Toll-like receptor 9 (TLR9), respectively—act together to sense DNA-containing antigens. The answer was not obvious because BCRs are thought to act primarily on the cell surface, whereas TLR9 is normally present on endocytic vesicles. In mouse B cells in which the BCR was activated, TLR9 was relocated into autophagosomes. When cells were stimulated only through TLR9 with unmethylated DNA, p38 mitogen-activated protein kinase was detected only in endosomes. However, if the BCR was activated with an antibody to immunoglobulin M (alone or with DNA to activate TLR9), p38 was detected in large autophagosome-like structures. The recruitment of TLR9 to this compartment depended on physical internalization of the BCR, and activation of phospholipase D was also necessary. — LBR

Immunity 28, 799 (2008).

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