Requirement for CARMA1 in antigen receptor-induced NF-kappa B activation and lymphocyte proliferation

Curr Biol. 2003 Jul 15;13(14):1252-8. doi: 10.1016/s0960-9822(03)00491-3.


Ligation of antigen receptors (TCR, BCR) on T and B lymphocytes leads to the activation of new transcriptional programs and cell cycle progression. Antigen receptor-mediated activation of NF-kappa B, required for proliferation of B and T cells, is disrupted in T cells lacking PKC theta and in B and T cells lacking Bcl10, a caspase recruitment domain (CARD)-containing adaptor protein. CARMA1 (also called CARD11 and Bimp3), the only lymphocyte-specific member in a family of membrane-associated guanylate kinase (MAGUK) scaffolding proteins that interact with Bcl10 by way of CARD-CARD interactions, is required for TCR-induced NF-kappa B activation in Jurkat T lymphoma cells. Here we show that T cells from mice lacking CARMA1 expression were defective in recruitment of Bcl10 to clustered TCR complexes and lipid rafts, in activation of NF-kappa B, and in induction of IL-2 production. Development of CD5(+) peritoneal B cells was disrupted in these mice, as was B cell proliferation in response to both BCR and CD40 ligation. Serum immunoglobulin levels were also markedly reduced in the mutant mice. Together, these results show that CARMA1 has a central role in antigen receptor signaling that results in activation and proliferation of both B and T lymphocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology*
  • Blotting, Southern
  • Blotting, Western
  • CARD Signaling Adaptor Proteins
  • Chromosome Mapping
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Expression Regulation*
  • Guanylate Kinases
  • Immunoglobulins / blood
  • Membrane Proteins
  • Mice
  • Mice, Mutant Strains
  • NF-kappa B / metabolism*
  • Nucleoside-Phosphate Kinase / immunology*
  • Nucleoside-Phosphate Kinase / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology*


  • Adaptor Proteins, Vesicular Transport
  • Apoptosis Regulatory Proteins
  • CARD Signaling Adaptor Proteins
  • Card11 protein, mouse
  • Immunoglobulins
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • Nucleoside-Phosphate Kinase
  • Guanylate Kinases