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The article discusses a study entitled "Disruption of Fnip1 reveals a metabolic checkpoint controlling B lymphocyte development," by H. Park and colleagues, which suggested that folliculin-interacting protein 1 (FNIP1) is required as a metabolic checkpoint for B cell maturation.

The article discusses two papers published in "Immunity" which describe the key role of the RAP and RAC2 GTPases in the formation of an immunological synapse. It cites the findings of "The Rap GTPases regulate B cell morphology, immune-synapse formation, and signaling by particulate B cell receptor ligands," by K.B.L. Lin and colleagues, and "Activation of the small GTPase Rec2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation," by E. Arana and colleagues.

E and inhibitor of DNA binding (ID) proteins are transcriptional regulators that function in many developmental processes in vertebrates and invertebrates. One subset of E proteins, the E2A proteins, have a central role in the transcriptional regulatory networks that promote commitment to and differentiation of the B- and T-cell lineages, and their function in these lineages is modulated by ID proteins. In this Review, I discuss recent studies that reveal a more extensive role for E and ID proteins in the transcriptional networks that drive the differentiation of many lymphoid lineages, as well as new functions for these proteins in haematopoietic stem cells and their multipotent, but lymphoid-primed, progeny. [ABSTRACT FROM AUTHOR]

The article presents information regarding adaptive immune system and the variants involved in Alzheimer disease(AD). Researchers used next generation sequencing technology to analyze B cell and T cell lymphopoiesis in blood samples from human fetuses. The data confirmed that B cell development precedes T cell development and this would define the immune competency. It was found that variants in TREM 2(triggering receptor expressed on myeloid cells 2) is associated with increased risk of AD.

The article reports on the findings of a study which suggests that BOB1 potentiates B cell receptor (BCR) signalling by regulating the expression of the microRNAs miR-146a and miR-210.

The article discusses the study by F. Montalvao and colleagues which describes the role of Kupffer cells in the of mechanism of anti-CD20 antibodies-mediated B cell depletion.

The article reports on a study which describes the expression of complement receptors of the follicular dendritic cells (FDCs) in acquiring complement-coated immune complexes from non-cognate B cells.

The article discusses the impact of B lymphocyte-induced maturation protein 1 (BLIMP1) in the cooling of keratinocytes in mice.

The article offers information on a new model for affinity maturation, wherein germinal centre B cells compete with their self secreted antibodies while accessing antigen. It discusses the effects of helminth infection, an intestinal disorder, in activating visceral adipose tissue resident group 2 innate lymphoid cells (VAT ILC2s) to produce interleukin-5 (IL-5) and IL-3. It highlights the use of intravital multiphoton microscopy in visualizing the spatiotemporal organization of immune cells.

The article offers information on the results of studies on phagocytes, protective role of innate-like B cells, and macrophage homeostasis.

The article offers information on the results of studies on inflammatory monocytes and neutrophils, B cells, and macrophages.

The article discusses the report on the role of class-switch recombination (CSR) on the developmental stages of B cells, which references the study "Immatue B cells prefeentially switch to IgE with increased direct Sµ to Sε recombination," by D. R. Wesemann and colleagues.

The article focuses on two studies published in the "Journal of Experimental Medicine," which show that interleukin-21 (IL-21) acts directly on B cells to promote their proliferation and retention in germinal centres. Studies by M. A. Linterman and colleagues, and by D. Zotos and colleagues found that mice lacking IL-21 showed defective antibody affinity maturation after immunization with T cell dependent antigens. Both showed IL-21 receptor signalling increases expression of B cell lymphoma 6.

The article discusses research being done on effect of B-cell tolerance on systemic lupus erythematosus (SLE). It references separate studies by K. R. Kumar et al and P. Pisitkun et al, in a 2006 issue of "Science." Pisitkun et al. studied the Y-chromosome-linked autoimmune accelerator locus, an SLE-susceptibility locus in mice. Kumar et al investigated the SLE1 locus, known to be another SLE-susceptibility locus in mice.

The article reports on the study of activation-induced cytidine deaminase (AID) for micro restraint(miR)-155-mediated suppression. AID starts the activation of somatic hypermutation and class switch recombination (CSR), thus regulates in the B cells. Furthermore, it removes the suppression of miR-155 in defective affinity maturation and induces oncogenic chromosomal translocation between Myc and Igh.

A letter to the editor in response to the article "Not always the bad guys: B cells as regulators of autoimmune pathology" in the 2008 issue is presented.

The article offers information on cytokine thymic stromal lymphopoietin (TSLP) and B-cell homeostasis in the U.S. TSLP is similar to interleukin-7 and is expressed by epithelial cells. TSLP is also known to stimulate B-cells development and there is increasing evidence that it has a role in allergic disease.

The article discusses research being done on B cell receptor (BCR) signaling and internalization. It references a study by P. Hou et al., published in a 2006 issue of the journal "PLoS Biology." Details of how the study was conducted are given. The study shows that BCR signalling and internalization events are mutually exclusive. The authors also determine that a small fraction of surface BCR complexes were phosphorylated.

Discusses research being done on the distinctiveness of Igm memory B cells from the classical germinal-center-derived memory B cells. Reference to a study by S. Weller et al, published in the 2004 issue of "Blood"; Contribution of the cells to the regulation of T-cell independent responses; Similarity of the composition of the memory cells with the phenotypic characteristic of the cells located in the splenic marginal zone.

Discusses research being done on the role of B-cell-specific transcription repressor BACH2 during class-switch recombination (CSR) and somatic hypermutation. Reference to a study by A. Muto et al., published in a 2004 issue of "Nature"; Results of an immunohistochemical analysis of transcription-factor expression; Discussion on BACH2 as a regulator of CSR.

Discusses research being done on B-cell receptor and Toll-like receptor cooperation in autoimmunity. Reference to a study by G. A. Vigilianti and colleagues published in a 2003 issue of "Immunity" journal; Explanation on how the autoreactive B cells involved in immune response are activated; Autoimmune mouse strain that produces B cells.

Cytokine production by B cells is important for multiple aspects of immunity. B cell-derived cytokines, including lymphotoxin, are essential for the ontogenesis, homeostasis and activation of secondary lymphoid organs, as well as for the development of tertiary lymphoid tissues at ectopic sites. Other B cell-derived cytokines, such as interleukin-6 (IL-6), interferon-γ and tumour necrosis factor, influence the development of effector and memory CD4+ T cell responses. Finally, B cells can regulate inflammatory immune responses, primarily through their provision of IL-10 and IL-35. This Review summarizes these various roles of cytokine-producing B cells in immunity and discusses the rational for targeting these cells in the clinic. [ABSTRACT FROM AUTHOR]

Over the past decade, a series of discoveries relating to fibroblastic reticular cells (FRCs) - immunologically specialized myofibroblasts found in lymphoid tissue - has promoted these cells from benign bystanders to major players in the immune response. In this Review, we focus on recent advances regarding the immunobiology of lymph node-derived FRCs, presenting an updated view of crucial checkpoints during their development and their dynamic control of lymph node expansion and contraction during infection. We highlight the robust effects of FRCs on systemic B cell and T cell responses, and we present an emerging view of FRCs as drivers of pathology following acute and chronic viral infections. Lastly, we review emerging therapeutic advances that harness the immunoregulatory properties of FRCs. [ABSTRACT FROM AUTHOR]

The immune system can remember a previously experienced pathogen and can evoke an enhanced response to reinfection that depends on memory lymphocyte populations. Recent advances in tracking antigen-experienced memory B cells have revealed the existence of distinct classes of cells that have considerable functional differences. Some of these differences seem to be determined by the stimulation history during memory cell formation. To induce rapid recall antibody responses, the contributions of other types of cells, such as memory T follicular helper cells, have also now begun to be appreciated. In this Review, we discuss these and other recent advances in our understanding of memory B cells, focusing on the underlying mechanisms that are required for rapid and effective recall antibody responses. [ABSTRACT FROM AUTHOR]

The development of B cells is dependent on the sequential DNA rearrangement of immunoglobulin loci that encode subunits of the B cell receptor. The pathway navigates a crucial checkpoint that ensures expression of a signalling-competent immunoglobulin heavy chain before commitment to rearrangement and expression of an immunoglobulin light chain. The checkpoint segregates proliferation of pre-B cells from immunoglobulin light chain recombination and their differentiation into B cells. Recent advances have revealed the molecular circuitry that controls two rival signalling systems, namely the interleukin-7 (IL-7) receptor and the pre-B cell receptor, to ensure that proliferation and immunoglobulin recombination are mutually exclusive, thereby maintaining genomic integrity during B cell development. [ABSTRACT FROM AUTHOR]

Basic leucine zipper transcription factor ATF-like (BATF), BATF2 and BATF3 belong to the activator protein 1 (AP-1) family of transcription factors, which regulate numerous cellular processes. Initially, BATF family members were thought to function only as inhibitors of AP-1-driven transcription, but recent studies have uncovered that these factors have unique, non-redundant and positive transcriptional activities in dendritic cells, B cells and T cells. The question of how BATF and BATF3 - which lack a transcriptional activation domain, unlike the AP-1 factors FOS and JUN - can exert unique positive transcriptional specificity has now been answered by the discovery that BATF molecules interact with members of the interferon-regulatory factor (IRF) family. The capacity of the BATF leucine zipper regions to mediate dimerization with AP-1 factors and also to define cooperative interactions with heterologous factors explains both the positive transcriptional activity of BATF proteins and how they activate distinct sets of target genes compared with FOS. [ABSTRACT FROM AUTHOR]

B cells are key components of the adaptive immune response. Their differentiation into either specific memory B cells or antibody-secreting plasma cells is a consequence of activation steps that involve the processing and presentation of antigens. The engagement of B cell receptors by surface-tethered antigens leads to the formation of an immunological synapse that coordinates cell signalling events and that promotes antigen uptake for presentation on MHC class II molecules. In this Review, we discuss membrane trafficking and the associated molecular mechanisms that are involved in antigen extraction and processing at the B cell synapse, and we highlight how B cells use cell polarity to coordinate the complex events that ultimately lead to efficient humoral responses. [ABSTRACT FROM AUTHOR]

?? T cells are a unique and conserved population of lymphocytes that have been the subject of a recent explosion of interest owing to their essential contributions to many types of immune response and immunopathology. But what does the integration of recent and long-established studies really tell us about these cells and their place in immunology? The time is ripe to consider the evidence for their unique and crucial functions. We conclude that whereas B cells and ?? T cells are commonly thought to contribute primarily to the antigen-specific effector and memory phases of immunity, ?? T cells are distinct in that they combine conventional adaptive features (inherent in their T cell receptors and pleiotropic effector functions) with rapid, innate-like responses that can place them in the initiation phase of immune reactions. This underpins a revised perspective on lymphocyte biology and the regulation of immunogenicity. [ABSTRACT FROM AUTHOR]

Protective responses to microorganisms involve the nonspecific but rapid defence mechanisms of the innate immune system, followed by the specific but slow defence mechanisms of the adaptive immune system. Located as sentinels at the interface between the circulation and lymphoid tissue, splenic marginal zone B cells rapidly respond to blood-borne antigens by adopting 'crossover' defensive strategies that blur the conventional boundaries of innate and adaptive immunity. This Review discusses how marginal zone B cells function as innate-like lymphocytes that mount rapid antibody responses to both T cell-dependent and T cell-independent antigens. These responses require the integration of activation signals from germline-encoded and somatically recombined receptors for microorganisms with helper signals from effector cells of the innate and adaptive immune systems. [ABSTRACT FROM AUTHOR]

The article presents a study that investigates the physiological significance of B cell in germinal B cell migration. As part of the study, the researchers have identified the mechanisms involved in B cell selection in germinal centers, and the importance of migration in dark and light zones. The study has also defined specific mechanism which govern B cell selection in germinal centers using a unique method with photoactivatable green fluorescent expression (PA-GFP).

The article highlights studies which have demonstrated the synergistic role of pro-apoptotic B-cell lymphoma 2 (BCL-2)- interacting mediator of cell death (BIM) and FAS receptor, also known as CD95 membrane glycoprotein, in the immune response in mice. It relates that BIM and FAS cooperate to regulate lymphocyte homeostasis, control lymphocyte numbers following chronic viral infection and prevent spontaneous autoimmunity.

Viral pathogens often induce strong effector CD4+ T cell responses that are best known for their ability to help B cell and CD8+ T cell responses. However, recent studies have uncovered additional roles for CD4+ T cells, some of which are independent of other lymphocytes, and have described previously unappreciated functions for memory CD4+ T cells in immunity to viruses. Here, we review the full range of antiviral functions of CD4+ T cells, discussing the activities of these cells in helping other lymphocytes and in inducing innate immune responses, as well as their direct antiviral roles. We suggest that all of these functions of CD4+ T cells are integrated to provide highly effective immune protection against viral pathogens. [ABSTRACT FROM AUTHOR]

Discusses research being done on the transcriptional repressor B-lymphocyte-induced maturation protein 1 (BLIMP1). Reference to the studies by G. A. Martins et al and A. Kallies et al published in the March 26, 2006 issue of "Nature Immunology"; Role of BLIMP1 in regulating T-cell homeostasis and activation; Results of experiments which aimed to determine the function of BLIMP1 in cell types other than B cells.

Discusses research being done on lymphocyte signaling. Reference to a study by K. Sommer et al., published in the 2005 issue of "Immunity"; Consequences of the ligation of cell-surface antigen receptors; Functions of protein kinase Β in B cells.

The existence of IgM has been known for more than a century, but its importance in immunity and autoimmunity continues to emerge. Studies of mice deficient in secreted IgM have provided unexpected insights into its role in several diverse processes, from B cell survival to atherosclerosis, as well as in autoimmunity and protection against infection. Among the various distinct properties that underlie the functions of IgM, two stand out: its polyreactivity and its ability to facilitate the removal of apoptotic cells. In addition, new B cell-targeted therapies for the treatment of autoimmunity have been shown to cause a reduction in serum IgM, potentially disrupting the functions of this immunoregulatory molecule and increasing susceptibility to infection. [ABSTRACT FROM AUTHOR]

B cells are essential for humoral immunity, but the role that they have in regulating CD4(+) T cell responses remains controversial. However, new data showing that the transient depletion of B cells potently influences the induction, maintenance and reactivation of CD4(+) T cells, with the recent identification of antibody-independent functions of B cells, have reinvigorated interest in the many roles of B cells in both infectious and autoimmune diseases. In this Review, we discuss recent data showing how effector and regulatory B cells modulate CD4(+) T cell responses to pathogens and autoantigens. [ABSTRACT FROM AUTHOR]

Immunological memory is a hallmark of the adaptive immune system. Plasma cells and memory B and T cells collectively provide protective immunity and effective secondary immune responses to invading pathogens. Here, we discuss how mesenchymal stromal cells regulate immunological memory by organizing defined numbers of dedicated survival niches for plasma cells and memory T cells in the bone marrow and also, to a lesser extent, in secondary lymphoid organs. An understanding of the biology of mesenchymal stromal cells and their interaction with cells of the immune system is key to fully understanding immunological memory. [ABSTRACT FROM AUTHOR]

Discusses research being done on the role of B and T-lymphocyte attenuator (BTLA) in regulating T cell activation with herpesvirus entry mediator (HVEM). Reference to a study by J. R. Sedy et al, published in the 2005 issue of "Nature Immunology"; Impact of the binding of BTLA and HVEM on tyrosine phosphorylation activity of BTLA; Importance of the interaction between BTLA and HVEM to regulate lymphocyte activation and homeostasis.

In germinal centres, somatic hypermutation and B cell selection increase antibody affinity and specificity for the immunizing antigen, but the generation of autoreactive B cells is an inevitable by-product of this process. Here, we review the evidence that aberrant selection of these autoreactive B cells can arise from abnormalities in each of the germinal centre cellular constituents--B cells, T follicular helper cells, follicular dendritic cells and tingible body macrophages--or in the supply of antigen. As the progeny of germinal centre B cells includes long-lived plasma cells, selection of autoreactive B cells can propagate long-lived autoantibody responses and cause autoimmune diseases. Elucidation of crucial molecular signals in germinal centres has led to the identification of novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Bone marrow-derived B cells make an important cell fate choice to develop into either follicular B cells or marginal zone B cells in the spleen, which depends on signalling through the B cell receptor, Notch2, the receptor for B cell-activating factor and the canonical nuclear factor-kappaB pathway, as well as signals involved in the migration and anatomical retention of marginal zone B cells. Recent information discussed in this Review reconciles some of the controversies regarding the role of the B cell receptor in this cell fate decision and a clearer picture has also emerged regarding the anatomical location of ligands for Notch2 in the spleen. This cell fate decision could provide mechanistic insights that are relevant to other commitment events in lymphocytes. [ABSTRACT FROM AUTHOR]

The seminal studies characterizing T follicular helper (T(FH)) cells described a non-polarized CD4(+) T cell population with a unique ability to home to B cell follicles and to induce antibody production by B cells. In the past few years, the study of T(FH) cells has enjoyed a renaissance and there has been a surge of research activity aimed at understanding the function and differentiation of these important cells. This Review focuses on the current progress in T(FH) cell biology and the important questions that remain unanswered. Particular attention is paid to recent studies that support the idea that T(FH) cells are a separate T cell lineage and those that probe the relationship of T(FH) cells to other T helper cell subsets. [ABSTRACT FROM AUTHOR]

Rho family GTPases, and the proteins that regulate them, have important roles in many cellular processes, including cell division, survival, migration and adhesion. Although most of our understanding of these proteins has come from studies using cell lines, more recent gene targeting studies in mice are providing insights into the in vivo function of these proteins. Here we review recent progress revealing crucial roles for these proteins in lymphocyte development, activation, differentiation and migration. The emerging picture shows that Rho family GTPases transduce signals from receptors for antigens, chemokines and cytokines, as well as adhesion molecules and pattern recognition receptors, and that they function as focal points for crosstalk between different signalling pathways. [ABSTRACT FROM AUTHOR]

The tumour necrosis factor (TNF) family members B cell activating factor (BAFF) and APRIL (a proliferation-inducing ligand) are crucial survival factors for peripheral B cells. An excess of BAFF leads to the development of autoimmune disorders in animal models, and high levels of BAFF have been detected in the serum of patients with various autoimmune conditions. In this Review, we consider the possibility that in mice autoimmunity induced by BAFF is linked to T cell-independent B cell activation rather than to a severe breakdown of B cell tolerance. We also outline the mechanisms of BAFF signalling, the impact of ligand oligomerization on receptor activation and the progress of BAFF-depleting agents in the clinical setting. [ABSTRACT FROM AUTHOR]

The relative importance of the intrinsic and extrinsic apoptotic pathways in the control of haematopoietic cell homeostasis has been a matter of debate for many years. Cell death is omnipresent in this cellular compartment and ensures the removal of cells that are not properly equipped to assume their function as well as those that have assumed function but are no longer required. In this Review we focus on the roles of CD95 (also known as FAS) and BCL-2-interacting mediator of cell death (BIM), two major regulators of apoptosis in T cell homeostasis, with a particular emphasis on their cooperation in the shutdown of T cell responses. [ABSTRACT FROM AUTHOR]

Many models of haematopoiesis dictate that haematopoietic stem cells make an early and irrevocable choice between lymphoid and myeloid cell fates. However, recent data show that intermediate progenitors have both lymphoid and myeloid potential, thereby refuting early theories and leading to a lack of consensus in the field. In this Opinion article we present a simple pairwise relationships model of cell fate determination that does not depend on the underlying developmental branch points that in other models dictate a preferred route (or routes) to a particular cell fate. [ABSTRACT FROM AUTHOR]

The pre-B-cell receptor (pre-BCR) is expressed following the productive recombination of the immunoglobulin heavy chain gene. Signals through the pre-BCR are required for initiating diverse processes in pre-B cells, including proliferation and recombination of the light chain gene, which eventually lead to the differentiation of pre-B cells to immature B cells. However, the molecular mechanisms by which the pre-BCR promotes these processes remain largely unresolved. Recent findings suggest that forkhead box O (FOXO) transcription factors connect pre-BCR signalling to the activation of the recombination machinery. In this Review, we discuss how FOXO transcription factors are regulated by the pre-BCR to allow the progression of the cell cycle and the recombination of the light chain gene. [ABSTRACT FROM AUTHOR]

Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirements. Inducing potent and sustained B-cell responses is as challenging in infants as it is in older subjects. Several mechanisms to explain the decreased B-cell responses at the extremes of age apply to both infants and the elderly. These include intrinsic B-cell limitations as well as numerous microenvironmental factors in lymphoid organs and the bone marrow. This Review describes the mechanisms that shape B-cell responses at the extremes of age and how they could be taken into account to design more effective immunization strategies for these high-risk age groups. [ABSTRACT FROM AUTHOR]

A functional immune system depends on the appropriate activation of lymphocytes following antigen encounter. In this Review, we summarize studies that have used high-resolution imaging approaches to visualize antigen presentation to B cells in secondary lymphoid organs. These studies illustrate that encounters of B cells with antigen in these organs can be facilitated by diffusion of the antigen or by the presentation of antigen by macrophages, dendritic cells and follicular dendritic cells. We describe cell-surface molecules that might be important in mediating antigen presentation to B cells and also highlight the key role of B cells themselves in antigen transport. Data obtained from the studies discussed here highlight the predominance, importance and variety of the cell-mediated processes that are involved in presenting antigen to B cells in vivo. [ABSTRACT FROM AUTHOR]

Discusses research being done on activation-induced cytidine deaminase provided by replication protein A. Reference to a study by J. Chaudhuri et al published in the July 25, 2004 issue of "Nature"; Description of somatic hypermutation (SHM); Mechanism by which SHM is a B-cell specific event.

Discusses research being done on the induction of T cell development and establishment of T cell competence from embryonic stem cells differentiated in vitro. Role of the Notch signalling pathway in determining whether lymphocyte progenitors become T or B cells; Determination of whether T cells generated on OP9-DL1 cells were functional in vivo and could reconstitute immunodeficient mice.