News & Views in 2001

Specialized mouse DCs exist that can recognize the presence of viral pathogens. New evidence shows that these DCs respond by secreting massive amounts of type I IFNs, which may provoke systemic resistance to such pathogens.

How immature CD4⁺CD8⁺ thymocytes become committed to either the CD4 (helper) or CD8 (cytotoxic) lineage is controversial. Genetic ablation of a silencer element in the gene encoding CD4 provides new evidence that CD8 lineage commitment occurs via a stochastic, rather than instructive, mechanism.

Generation of intestinal secretory IgA depends on antigen induction of B cells in organized GALT. A recent paper in Nature reports that in mice the lamina propria provides signals that direct mucosal B cells to undergo C_α class switching and as a basis for SIgA production.

A new family of conserved genes encodes mucin-like glycoproteins. These genes contribute to asthma susceptibility by influencing T_H differentiation and cytokine production.

New evidence suggests that mediators of T cell quiescence and immune suppression converge on a common transcriptional program. Tob, a member of a family of anti-proliferation regulators, actively maintains T cell quiescence by interacting with components of the TGF-β signal transduction pathway.

Is a lifetime of sequential viral infections detrimental or advantageous to the host? New evidence suggests that pre-existing memory T cells specific for one type of virus can alter, for the better, the disease outcome after infection with an unrelated virus.

Regulation of the transcription factor Shn-2 by signals emanating from the TCR can distinguish positive from negative selection of developing thymocytes.

Viruses, such as CMV, have evolved a number of strategies with which to evade the immune system. Evidence is now emerging that murine CMV can also suppress the immune response by inducing functional paralysis of DCs.

The “two-signal” model proposes that immature DCs that deliver signal 1 in the absence of signal 2 cross-tolerize CD8⁺ T cells. New evidence shows that mature DCs are required for both cross-tolerance and cross-priming.

All kinases must be tightly regulated. Isolation of a novel molecule called IBtk identifies a potential mechanism for the regulation of Bruton's tyrosine kinase in B cells.

The T_H1-T_H2 paradigm, in which CD4⁺ T cells polarize into type 1 or type 2 helper cells, has been extended to other cells types. However, evidence now suggests that NK cells differentiate sequentially from immature type 2 to mature type 1 cells, a pathway that could apply to other lymphocytes.

Hypermutation and gene conversion appear to be distinct mechanisms that can explain somatic diversification of the antibody repertoire. Data in a recent Nature paper suggest unappreciated links between the two.

Most receptors transmit extracellular signals to the cytoplasm, but integrins can also be stimulated in the reverse direction. A recent pair of Science papers report that “inside-out” signaling from the TCR is mediated by a newly identified protein called SLAP-130 or Fyb.

Successful passage through several developmental checkpoints determines whether thymocytes survive, proliferate or differentiate. New data show that Wnt-frizzled–induced activation of TCF-1 or Lef-1, via their coactivator β-catenin, is critical during TCRB and TCRA gene rearrangement in thymocytes.

Individual lymphocytes express antigen receptors of a singular specificity. How this process, known as allelic exclusion, is established and maintained is unknown. Differences in subnuclear localization appear to contribute to enforcement of monoallelic receptor expression.

The pathogenesis of multiple sclerosis consists of an inflammatory and neurodegnerative phase. Better understanding of these stages has aided the development of specific therapeutic targets.

B cells can regulate many aspects of immune reactivity, as well as differentiate into antibody-producing cells. In SLE, a systemic autoimmune disease, recent research suggests enhanced B cell function is the defining pathogenic event.

The era of genomic-wide sequence analysis promises to yield new insights in global regulatory gene control. Comparative genome studies have identified a critical regulator of T_H2 cytokine expression.

Dendritic cells can prime naïve lymphocytes. New data show how dendritic cells provide early activation cues by expression of IL-2, which may greatly enhance both T and B cell responses.