T cell development and effector function depends on signaling initiated via the T cell antigen receptor (TCR). Nature Immunologypresents a focus on TCR signaling with four specially commissioned Review and Perspective articles.

A series of Reviews specially commissioned by Nature Immunologydiscuss post-transcriptional and post-translational modifications in the immune system. The Focus covers the role of such modifications in various aspects of the immune system ranging from development to activation to immunopathology.

New technologies enable analysis of the extraordinarily diverse and polymorphic components of the immune system–especially the human immune system–at a level of unprecedented detail. Reviews and a Commentary specially commissioned by Nature Biotechnology and Nature Immunology discuss these new methodologies, and how they may be applied to track immune status in health and disease, as well as to reveal new basic immunological insight. A Correspondence describing an initiative to design tools and resources to facilitate these high-dimensional analyses is also included.

A web focus from Cell Death & Differentiation, Cell Death & Disease, Nature Immunology and Oncogene. We hope you enjoy this focus including work from the world's most recognized experts in the field of Necroptosis.

Immune cells are found in diverse nonlymphoid tissues where they patrol against infection and injury and help to maintain homeostasis. This month's Focus features five specially commissioned Reviews that discuss interactions and functions of tissue-resident leukocytes.

Six specially commissioned Reviews and Perspectives discuss specific aspects of the interaction between the microbiota and the immune system and their influence on local and systemic immune homeostasis.

NK cells, which play important roles in homeostasis, surveillance and defense, the three major functions of the immune system, were first observed in 1975, 20 years after the discovery of T and B lymphocytes. Despite almost 40 years passing, our understanding of NK cell immunology in general lags far behind that of T and B lymphocytes. However, over the past 5 years, significant progress has been made in understanding NK cell biology.

Over the past several decades, significant progress has been made in understanding the roles of B cells in immunity and autoimmunity. B-cell development, occurring in the bone marrow, is a complex dynamic process involved in immunoglobulin (Ig) gene rearrangement and B-cell receptor (BCR) expression. Early progenitor B (pro-B) cells initiate DNA rearrangement at their Ig heavy chain loci, resulting in the synthesis of m-chains in the cytoplasm and the assembly of the precursor B-cell receptor (pre-BCR). Following the successful rearrangement of light chain genes, these precursor B (pre-B) cells differentiate into immature B cells when whole IgM molecules are expressed as functional BCR on the cell surface. The newly formed immature B cells then leave the bone marrow and become mature B lymphocytes in the peripheral lymphoid organs.

Five specially commissioned reviews and commentaries discuss the metabolic requirements of immune responses and the regulatory circuits that balance eradication of the pathogen with minimal collateral damage to the host.

Follicular helper T cells (TFH) are able to closely interact with B cells to promote the formation of germinal centers (GCs). The stable cognate interaction between TFH and B cells in the GC is mutually beneficial to both cells for their development and function. Specifically, help B cells produce long-lived memory B cells and high-affinity antibodies and, in reciprocation, TFH cells are helped by B cells for further differentiation through cell cognation. This results in effective antibody responses to provide protection against pathogenic microbes. This focus presents links to related articles from across Springer Nature to provide more background information about these cells.

A comprehensive overview, and four review articles examine activation, regulation and function of the inflammasome.

The January 2012 special issue presents two important strategies for generating potent and lasting anti-tumor immunity. The first strategy is to subvert immune suppressive networks in the tumor microenvironment. The second strategy is to optimize conventional and anti-biological modalities to directly target tumor and adjacent tumor tissue, and mobilize and expand anti-tumor immunity in the tumor microenvironment which results in tumor eradication. Further background information on this important topic is available through the accompanying web focus which links to related articles from across Springer Nature.