Immune responses

Constitutive expression of the B7h ligand for inducible costimulator on naive B cells is extinguished after activation by distinct B-cell receptor- and interleukin-4 receptor-mediated pathways and can be rescued by CD40 signaling.Liang, L., Porter, E. M. & Sha, W. C. J. Exp. Med. 196, 97–108 (2002)

The ligand–receptor pair of B7h and inducible co-stimulator (ICOS) provides essential co-stimulation for antibody responses. The expression of ICOS is induced on activated T cells and B7h is expressed constitutively by naive B cells. This study shows that interleukin-4 and the B-cell receptor transduce distinct signals that synergise for the inhibition of B7h expression. CD40 signals, however, reverse this down-regulation of expression. So, the re-induction of B7h expression on activated B cells by CD40 might be an important checkpoint to ensure productive cognate B-cell–T-cell interactions at later stages of the B-cell response.

B-Cell development

Reversion of B-cell commitment upon loss of Pax5 expression.Mikkola, I. et al. Science 297, 110–113 (2002)

The transcription factor Pax5 is essential for the initiation of B-cell development, but its role in maintaining that cell-fate decision is unknown. In this study, Pax5 was inactivated in purified mouse pro-B cells, which are committed to the B-cell lineage. The pro-B cells continued to divide, but began to lose expression of B-cell lineage-specific genes, whereas genes that are specific for other lineages were turned on. Under the appropriate culture conditions, the Pax5-deficient pro-B cells generated fully mature macrophages, and when injected into recombination-activating gene 2 (Rag2)−/− mice, they could also give rise to T cells. So, continuous expression of Pax5 during early B-cell development is essential for the maintenance of commitment to the B-cell lineage.

Immune regulation

IL-4-dependent alternatively activated macrophages have a distinctive in vivo gene-expression phenotype.Loke, P. et al. BMC Immunol. 3, 7 (2002)

This study provides the first functional genomic characterization of alternatively activated macrophages that are generated in vivo. The term 'alternatively activated' was used inititally to describe macrophages that are activated in vitro, in the presence of T-helper 2 cytokines. These cells fail to express inflammatory effector molecules, but their role in vivo is unclear. Previously, this group showed that macrophages from mice that are infected with the nematode Brugia malayi have a potent suppressive activity that is interleukin-4 (IL-4)-dependent. Here, the gene-expression profile of these suppressive macrophages was determined by various approaches. Interestingly, Fizz1 and Ym1 — genes that have been associated previously with lung inflammation — were identified as major IL-4-regulated genes in these cells.