Volume 10 Issue 4, April 2009

How immunoglobulin gene loci are specifically targeted by activation-induced cytidine deaminase while the rest of the genome avoids potentially mutagenic events is becoming clearer.

Two papers published recently in Science exploit new transgenic mouse systems to explore the path that activated CD8⁺ T cells take on the way to memory differentiation.

Antibody responses are critical for host protection against many pathogens. By reporting what actually occurs in vivo, two new studies provide important clues about follicular helper T cells that are dedicated to providing help to B cells.

Efficient humoral immunity requires B cell–T cell interactions in lymphoid follicles. McHeyzer-Williams and colleagues show that CXCR5⁺ follicular helper T cells have T cell antigen receptors with higher affinity for antigen than do other responding effector helper T cells.

High-affinity isotype-switched B cells arise in germinal centers. Locksley and colleagues show that follicular helper T cells are the main cytokine providers for GC B cells and thereby directly influence the ensuing antibody response.

Lymphocytes are typically recruited into lymph nodes via CCR7. Gunn and colleagues identify an 'inflammatory DC' subset that is recruited directly from the bloodstream through the use of CCR2 and that induces potent T helper type 1 priming.

The molecular mechanisms that govern B cell progenitor localization in bone marrow sinusoids are not understood. Cyster and colleagues demonstrate involvement of cannabinoid receptor 2 in retaining developing B cells in sinusoids.

The function of the CD98hc transmembrane protein in adaptive immune responses has been unclear. Ginsberg and colleagues show that CD98hc is needed for B cell proliferation and subsequent plasma cell differentiation.

Immunoglobulin class-switch recombination requires activation-induced cytidine deaminase. Chaudhuri and colleagues show independent recruitment of protein kinase A to switch regions, where it phosphorylates this deaminase to promote class-switch recombination.

In peripheral lymphoid organs, γδ T cells are a source of interleukin 17. Silva-Santos and colleagues find that production of interleukin 17 versus interferon-γ by γδ T cells is inflexible and is determined in the thymus.

Toll-like receptors (TLRs) induce complex transcriptional responses. Aderem and colleagues use systems-biology approaches to show that three transcription factors, NF-κB, ATF3 and C/EBPδ, work together to distinguish persistent versus transient TLR stimuli.

An overview, three review articles and two perspective articles cover the complex interplay among signaling pathways operative in immune cells.