In Brief

B-cell development

CD22 regulates early B-cell development in BOB.1/OBF.1-deficient mice.Samardzic, T. et al. Eur. J. Immunol. 32, 2481–2489 (2002)

In the absence of the B-cell-specific transcriptional co-activator BOB.1, mice have reduced numbers of mature B cells due to a block at the transitional B-cell stage. In this study, Samardzic et al. show that expression of the inhibitory co-receptor CD22 by B-cell precursors is increased in the bone marrow of BOB.1^−/− mice. The authors generated BOB.1^−/−Cd22^−/− double knock-out mice; they show that they have normal B-cell development in the bone marrow and that Ca²⁺ mobilization in response to B-cell-receptor (BCR) stimulation is restored in mature B cells. Together, these experiments indicate that the increased expression of CD22 in BOB.1^−/− mice acts as a brake on BCR signalling, which blocks B-cell development at the transitional stage.

Autoimmunity

Cblb is a major susceptibility gene for rat type-1 diabetes mellitus.Yokoi, N. et al. Nature Genet. 31, 391–394 (2002)

Insulin-dependent diabetes mellitus (IDDM) results from the complex interplay of many genetic and environmental susceptibility factors. Several animals spontaneously develop a disease that is similar to IDDM and they are useful models in which to unravel the complex aetiology of this disease. Previous studies of the Komeda diabetes-prone (KDP) rat have identified two main susceptibiltiy loci — the MHC and Iddm/kdp1 loci. By comparing mouse and rat backcrosses, the authors were able to place Iddm/kdp1 in a 3.0 cM segment, and two genes were then mapped to this locus. One of these genes — Cblb (Casitas B-lineage lymphoma b) — contained a nonsense mutation in KDP rats. The diabetic phenotype of the KDP rat was completely rescued by a wild-type Cblb transgene, which confirms that an absence of Cblb is the prinicipal cause of diabetes in KDP rats.

Asthma

Antigen-specific regulatory T cells develop via the ICOS–ICOS-ligand pathway and inhibit allergy-induced airway hyperreactivity.Akbari, O. et al. Nature Med. 29 July 2002 (DOI 10.1038/nm745)

Uncontrolled T helper 2 (T_H2) responses in the lung lead to the development of asthma and allergy, so how are they controlled normally? In this study, Akbari and colleagues show that after intranasal exposure to the model antigen ovalbumin, mouse lung dendritic cells produce interleukin-10 (IL-10) and can prime transgenic ovalbumin-specific T cells in vitro to become IL-10-secreting regulatory T (T_R) cells. When the T_R cells were transferred into mice, they markedly inhibited the development of T_H2 responses and ovalbumin-induced airway hyperreactivity. In addition to IL-10, the development of T_R cells depended crucially on the ICOS–ICOS-ligand co-stimulatory pathway.