Reviews & Analysis

Immunoglobulins secreted by memory B cells dominate secondary humoral responses. New evidence suggests the cytoplasmic tails of BCRs confer an advantage to cells expressing IgG, leading to their sustained proliferation and immunoglobulin production

Leukocyte arrest on inflamed endothelium constitutes only the first phase of their recruitment into the tissues. New data points to the roles played by JAM-1 and CD99 in leukocyte passage through the barrier posed by the vascular endothelium during inflammatory responses.

T cells bearing two different TCRs can be detrimental because the unselected TCR has the potential to cause autoimmunity. Evidence is now emerging that the unselected TCR may also be beneficial by expanding the TCR repertoire for foreign antigens.

Conventional CD8αβ participates in the activation of T cells by binding to the same peptide-MHC complex as does the TCR. A recent paper in Science shows, however, that the CD8αα form on iIELs binds TL and could alter signals from the TCR.

Spacial organization of membrane components can facilitate productive interactions between T cells and APCs. New data suggest that specific peptides are clustered within APC tetraspan microdomains that are more efficient in evoking T cell responses.

Multiple regulatory cascades control inflammatory gene expression. The responsive loci need to be prepared to bind the inducing regulatory factors, and such changes can be invoked by p38-dependent histone modification.

Activation of T cells requires TCR engagement of foreign peptide complexed with MHC. New evidence suggests that TCR engagement of self-peptide–MHC complexes may enhance recognition of foreign antigen.

Distinguishing which antigen-specific T cell clones will give rise to secondary immune responses is a subject of debate. New data shows higher affinity T cells are better competitors because they are activated more efficiently and can induce the loss of peptide-MHC from DCs.

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.