-
Trends in Immunology Dec 2001
Topics: Animals; Autoimmune Diseases; B-Lymphocytes; Cell Differentiation; Cell Movement; Gene Rearrangement, B-Lymphocyte; Genetic Predisposition to Disease; Humans; Immunologic Memory; Receptors, Antigen, B-Cell; Signal Transduction
PubMed: 11738977
DOI: 10.1016/s1471-4906(01)02052-x -
Annual Review of Immunology Apr 2020B cells are traditionally known for their ability to produce antibodies in the context of adaptive immune responses. However, over the last decade B cells have been... (Review)
Review
B cells are traditionally known for their ability to produce antibodies in the context of adaptive immune responses. However, over the last decade B cells have been increasingly recognized as modulators of both adaptive and innate immune responses, as well as players in an important role in the pathogenesis of a variety of human diseases. Here, after briefly summarizing our current understanding of B cell biology, we present a systematic review of the literature from both animal models and human studies that highlight the important role that B lymphocytes play in cardiac and vascular disease. While many aspects of B cell biology in the vasculature and, to an even greater extent, in the heart remain unclear, B cells are emerging as key regulators of cardiovascular adaptation to injury.
Topics: Adaptive Immunity; Animals; B-Lymphocytes; Cardiovascular Diseases; Cytokines; Disease Susceptibility; Humans; Immunity, Innate; Inflammation Mediators
PubMed: 32340574
DOI: 10.1146/annurev-immunol-042617-053104 -
Seminars in Immunology Jun 2003Among the transcriptional mediators of the various signal transduction pathways that have been shown to regulate lymphocyte apoptosis, Rel/NF-kappaB transcription... (Review)
Review
Among the transcriptional mediators of the various signal transduction pathways that have been shown to regulate lymphocyte apoptosis, Rel/NF-kappaB transcription factors have emerged as key regulators of B cell survival during their differentiation and in their activation by antigens or mitogens. The aim of this review is to bring together recent findings on Rel/NF-kappaB regulation of B cell survival and to present an integrated model of how these transcription factors control apoptosis in a signal and differentiation-stage specific manner. In addition to providing a contemporary view of Rel/NF-kappaB regulated B cell survival, the model described here is aimed to serve as a paradigm for how Rel/NF-kappaB family members control survival in different cell types during differentiation and in response to the plethora of signals that impinge on this master transcriptional regulatory pathway.
Topics: Animals; B-Lymphocytes; Cell Survival; NF-kappa B; Proto-Oncogene Proteins; Signal Transduction; Transcription Factor RelB; Transcription Factors
PubMed: 14563114
DOI: 10.1016/s1044-5323(03)00036-8 -
Philosophical Transactions of the Royal... Aug 1994Apoptosis (programmed cell death) has been suggested to be involved in clonal elimination of self-reactive lymphocytes for the normal function of the immune system. By... (Review)
Review
Molecular mechanisms for B lymphocyte selection: induction and regulation of antigen-receptor-mediated apoptosis of mature B cells in normal mice and their defect in autoimmunity-prone mice.
Apoptosis (programmed cell death) has been suggested to be involved in clonal elimination of self-reactive lymphocytes for the normal function of the immune system. By crosslinking the antigen receptor (surface immunoglobulin; sIg) on the peritoneal B cells of normal mice, we found that strong crosslinking of sIg induces apoptosis of mature B cells, suggesting that interaction with membrane-bound self-antigens may eliminate self-reactive mature B cells by apoptosis. Antigen-receptor-mediated B cell apoptosis is blocked when a signal is transduced via the CD40 molecule on the B cell surface. Because the ligand of CD40 (CD40L) is expressed on activated T helper cells, B cells may escape from apoptosis and are activated when the immune system interacts with foreign antigens, which are normally able to activate T helper cells. Moreover, sIg crosslinking fails to induce apoptosis of both bcl-2-transgenic mice and autoimmune-disease-prone New Zealand mice. In these mice, the defect in sIg-mediated apoptosis of mature B cells may allow generation of self-reactive B cells, resulting in pathogenic consequences.
Topics: Animals; Antigens; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Apoptosis; Autoimmunity; B-Lymphocytes; CD40 Antigens; Mice; Mice, Inbred C57BL; Receptors, Antigen, B-Cell
PubMed: 7531346
DOI: 10.1098/rstb.1994.0109 -
Biochemical Society Transactions Apr 2004PI3K (phosphoinositide 3-kinase) family members control a variety of cellular responses, such as cell growth, survival, cytoskeletal remodelling and the trafficking of... (Review)
Review
PI3K (phosphoinositide 3-kinase) family members control a variety of cellular responses, such as cell growth, survival, cytoskeletal remodelling and the trafficking of intracellular organelles, in many cell types, including lymphocytes. It has been difficult to evaluate the roles of distinct PI3Ks in immune responses, because specific inhibitors for each PI3K are lacking and most stimuli activate multiple PI3Ks. The development of gene-targeted mice has now allowed the elucidation of roles played in vivo by PI3K species in the immune system. Studies on mice deficient in catalytic as well as regulatory subunits of class IA PI3Ks have shown the importance of this class of PI3K in B lineage cells. Here I discuss the role of class IA PI3Ks in B lymphocyte development and B cell antigen receptor-mediated signal transduction.
Topics: Agammaglobulinaemia Tyrosine Kinase; Animals; B-Lymphocytes; Catalysis; Cell Division; Cytoskeleton; Humans; Mice; Mice, Knockout; Models, Biological; Phenotype; Phosphatidylinositol 3-Kinases; Protein Structure, Tertiary; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcr; Signal Transduction
PubMed: 15046599
DOI: 10.1042/bst -
Toxicological Sciences : An Official... Jul 2019Tungsten is an emerging environmental toxicant associated with several pediatric leukemia clusters, although a causal association has not been established. Our previous...
Tungsten is an emerging environmental toxicant associated with several pediatric leukemia clusters, although a causal association has not been established. Our previous work demonstrated that tungsten exposure resulted in an accumulation of pre-B cells in the bone marrow, the same cell type that accumulates in pediatric acute lymphoblastic leukemia (ALL). To better understand the relevant molecular mechanisms, we performed RNA-sequencing on flow sorted pre-B cells from control and tungsten-exposed mice. Tungsten decreased the expression of multiple genes critical for B cell development, including members of the interleukin-7 receptor (IL-7R) and pre-B cell receptor signaling pathways, such as Jak1, Stat5a, Pax5, Syk, and Ikzf3. These results were confirmed in an in vitro model of B cell differentiation, where tungsten arrested differentiation at the pro-B cell stage and inhibited proliferation. These changes were associated with decreased expression of multiple genes in the IL-7R signaling pathway and decreased percentage of IL-7R, phosphorylated STAT5 double-positive cells. Supplementation with IL-7 or overexpression of Pax5, the transcription factor downstream of IL-7R, rescued the tungsten-induced differentiation block. Together, these data support the hypothesis that IL-7R/Pax5 signaling axis is critical to tungsten-mediated effects on pre-B cell development. Importantly, many of these molecules are modulated in ALL.
Topics: Animals; B-Lymphocytes; Cell Differentiation; Cell Proliferation; Down-Regulation; Gene Expression; Male; Mice, Inbred C57BL; PAX5 Transcription Factor; Receptors, Interleukin-7; Signal Transduction; Tungsten Compounds
PubMed: 30912803
DOI: 10.1093/toxsci/kfz080 -
Seminars in Immunology May 1990B lymphocyte differentiation proceeds in the bone marrow in association with a supporting framework of stromal cells. The various long-term bone marrow cultures have... (Review)
Review
B lymphocyte differentiation proceeds in the bone marrow in association with a supporting framework of stromal cells. The various long-term bone marrow cultures have provided valuable in vitro models for the study of both normal and dysregulated, stromal cell dependent B lymphopoiesis. Stromal cell lines have been cloned from the adherent layers of the cultures, and recent studies indicate these cells produce soluble factors that control the growth and differentiation of B lineage cells. Modifications of the long-term cultures are now being developed that permit specific stages in the B cell developmental pathway to be amplified. These systems should prove valuable for analysis of stromal cell derived signals that regulate the growth and differentiation of B lineage cells.
Topics: Animals; B-Lymphocytes; Bone Marrow; Bone Marrow Cells; Calcitriol; Cell Differentiation; Cells, Cultured; Humans; In Vitro Techniques; Interleukin-1; Mice; Transforming Growth Factor beta
PubMed: 2129906
DOI: No ID Found -
Revista Alergia Mexico (Tecamachalco,... 2016B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B... (Review)
Review
B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.
Topics: Animals; B-Lymphocytes; Biological Evolution; Fishes; Humans; Invertebrates; Mice; Phylogeny
PubMed: 27174762
DOI: 10.29262/ram.v63i2.150 -
Advances in Experimental Medicine and... 2009The hallmark of B-cell development is the ordered recombination of immunoglobulin (Ig) genes. Recently, considerable progress has been achieved in assembling gene... (Review)
Review
The hallmark of B-cell development is the ordered recombination of immunoglobulin (Ig) genes. Recently, considerable progress has been achieved in assembling gene regulatory networks comprised of signaling components and transcription factors that regulate B-cell development. In this chapter we synthesize experimental evidence to explain how such signaling pathways and transcription factors can orchestrate the ordered recombination of immunoglobulin (Ig) genes. Recombination of antigen-receptor loci is regulated both by the developmentally controlled expression of the Rag1 and Rag2 genes and the accessibility of particular loci and their gene segments to recombination. A new framework has emerged that invokes nuclear compartmentalization, large-scale chromatin dynamics and localized changes in chromatin structure in regulating the accessibility of Ig loci at specific stages of B-cell development. We review this emergent framework and discuss new experimental approaches that will be needed to explore the underlying molecular mechanisms.
Topics: Alleles; Animals; B-Lymphocytes; Gene Rearrangement, B-Lymphocyte; Genes, Immunoglobulin; Immunoglobulin Light Chains; Immunoglobulin Variable Region; Recombination, Genetic; Signal Transduction; Transcription Factors
PubMed: 19731807
DOI: 10.1007/978-1-4419-0296-2_11 -
Arthritis Research & Therapy 2009B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have... (Review)
Review
B-cell development is tightly regulated, including the induction of B-cell memory and antibody-secreting plasmablasts and plasma cells. In the last decade, we have expanded our understanding of effector functions of B cells as well as their roles in human autoimmune diseases. The current review addresses the role of certain stages of B-cell development as well as plasmablasts/plasma cells in immune regulation under normal and autoimmune conditions with particular emphasis on systemic lupus erythematosus. Based on preclinical and clinical data, B cells have emerged increasingly as both effector cells as well as cells with immunoregulatory potential.
Topics: Animals; Autoimmune Diseases; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Cell Differentiation; Humans; Lymphocyte Activation
PubMed: 19849820
DOI: 10.1186/ar2780