Volume 15 Issue 3, March 2014

Progress in understanding the multifaceted biology of B cells and their multiple contributions to autoimmunity is providing productive understanding of disease pathogenesis and is leading to novel strategies for therapeutic intervention.

Hyperactivity of a branch of the unfolded protein response in CD8α⁺ dendritic cells degrades endoplasmic reticulum–associated mRNAs, which leads to a defect in the cross-presentation of dead cell–derived antigens.

Phosphorylation of the adhesion molecule VE-cadherin at tyrosine residues modulates the opening of endothelial junctions during inflammatory reactions. The replacement of two distinct residues in VE-cadherin shows that Tyr685 regulates vascular permeability and Tyr731 regulates leukocyte diapedesis in vivo.

Naive T cells differentiate into memory subsets upon exposure to their cognate foreign antigen. However, before such encounters, some naive T cells are 'imprinted' through their interactions with self targets.

The viability of long-lived plasma cells is enhanced by the expression of inducible nitric oxide synthase, which relieves endoplasmic reticulum stress by triggering a response dependent on cGMP and protein kinase G.

Tyrosine phosphorylation of VE-cadherin affects endothelial junction integrity. Vestweber and colleagues show that two different tyrosine residues distinctly and selectively regulate vascular permeability or leukocyte extravasation.

IL-1 triggers IRF1 signaling, but the biological importance of this has remained uncertain. Kordula and colleagues show that an IL-1–IRF1 pathway is necessary for the selective induction of chemokines and sterile inflammation.

The transcriptional repressor DREAM is involved in pain sensing. Tiruppathi and colleagues show that it is also involved in innate signaling by regulating the anti-inflammatory deubiquitinase A20.

The role of the unfolded protein response in the immune system is poorly understood. Lambrecht and colleagues show that CD8α⁺ DCs have a constitutively active component of this response that is important for their homeostatic function.

The transcriptional regulator Aire is required for central tolerance, but how it manages to target tissue-specific genes is unclear. Anderson and colleagues show that Aire achieves such targeting by coopting the ATF7ip-MBD1 repressor complex.

Interactions of the TCR with self peptide–MHC are crucial to T cell development. Allen and colleagues show that the strength of such interactions also determines the intrinsic T cell functionality and responses to pathogens.

Plasma cells must accommodate the cellular stress associated with antibody production. George and colleagues show that the survival of plasma cells requires inducible nitric oxide synthase (iNOS) to modulate the cellular ER stress response.

The transcription factor Ikaros is required for lymphopoiesis. Busslinger and colleagues show Ikaros positively regulates genes encoding pre-BCR signal transducers and thereby promotes pro-B to pre-B cell progression and proliferation.

Ikaros deletions are associated with certain human malignancies. Georgopoulos and colleagues show that loss of Ikaros arrests B lymphoid progenitors at an adherent and proliferative pre-B cell stage from which leukemia can arise.