Immunology

Lymphocyte Signaling on the CARDs

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Science  04 Jul 2003:
Vol. 301, Issue 5629, pp. 21
DOI: 10.1126/science.301.5629.21c

Antigen recognition by lymphocytes leads to the construction of membrane-associated complexes that mediate the signals that initiate the transcription of immune response genes. Caspase recruitment domain (CARD)-containing proteins, such Bcl10 and Carma1, help regulate this activity through contact with each other and with other members of the signaling complex.

Hara et al. found that Carma1-deficient mice were defective in natural killer (NK) and B cell development and displayed severely impaired receptor-mediated activation of downstream proteins NF-κB and JNK in T and B cells. Using genome-wide mutagenesis, Jun et al. disrupted Carma1 function via a point mutation, producing signaling defects similar to those seen in Carma1-deficient mice although T cell function was not as severely compromised. These animals also produced excessive IgE antibody and developed allergic skin pathology, suggesting that the partial T cell defect may have contributed to T helper cell dysfunction. Newton and Dixit, in mice expressing a CARD-less Carma1, observed similar defects in B and T cell proliferation. These studies reveal an unexpected level of versatility by Carma1 in coordinating the pathways required for lymphocyte activation. — SJS

Immunity 18, 763; 751 (2003); Curr. Biol. 10.1016/S0960982203004585 (2003).

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