T-cell development

Tox: an HMG box protein implicated in the regulation of thymocyte selection. Wilkinson, B. et al. Nature Immunol. 3, 272–280 (2002) [ PubMed ]

T-cell receptor (TCR) signalling is vital for the positive selection of mature T cells. How these signals are translated into changes in gene expression that are required for T-cell maturation and lineage commitment is unknown. This study describes the identification of Tox, which encodes an high mobility group (HMG) box family DNA-binding protein. Tox mRNA and protein are upregulated in T cells undergoing positive selection, and Tox transgenic mice have increased CD8+ and reduced CD4+ thymocytes. This perturbed lineage commitment might result from Tox-mediated changes in gene expression.

Somatic hypermutation

Activation-induced cytidine deaminase turns on somatic hypermutation in hybridomas. Martin, A. et al. Nature 415, 802–806 (2002) [ PubMed ]

Activation-induced cytidine deaminase (AID) is essential for somatic hypermutation, although its actual role is not understood. Here, hybridomas, which represent an antibody-secreting B-cell stage that does not normally undergo hypermutation, were transfected with AID. Surprisingly, this was sufficient to induce hypermutation of V genes, indicating that other factors expressed by germinal centre-stage B cells are not essential for the induction of hypermutation. This discovery opens up the possibility of recapitulating affinity maturation in vitro to improve the binding of monoclonal antibodies.

Lymphocyte migration

CXCL13 is required for B1-cell homing, natural antibody production and body cavity immunity. Ansel, K. M., Harris, R. B. & Cyster, J. G. Immunity 16, 67–76 (2002) [ PubMed ]

B1 cells predominate in the body cavities and participate in innate defence by producing natural antibody. Here the authors show that the chemokine CXCL13, which is essential for the homing of conventional (B2) B cells to B-cell follicles, is also crucial for the homing of B1 B cells to the peritoneum. CXCL13−/− mice lack peritoneal B1 cells and have reduced levels of natural antibody, as well as dimininshed responses to classic B1-cell ligands, such as phosphorylcholine. Two key sources of CXCL13 were identified — peritoneal macrophages and stromal cells within the omentum.