Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
24
5
2004
Effect of Age on the Immunoglobulin Class Switch
24
10.1615/CritRevImmunol.v24.i5.10
Daniela
Frasca
Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-138), Miami, FL33101
Richard L.
Riley
Department of Microbiology and Immunology, University of Miami School of Medicine, P.O. Box 016960 (R-138), Miami, FL33101
Bonnie B.
Blomberg
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA
Aging represents a complex remodelling in which both specific and innate immunity deteriorate. Age-related changes in humoral immunity involve reduced vaccine responses and increased production of auto-antibodies. Although T-cell alterations play a significant role in age-related humoral immune changes, alterations in B cells also occur. In this review, we provide an overview of age-related changes in B-cell functions and markers, including transcription factors, and also discuss controversies in the field of B-cell aging. We summarize our recent results, showing that splenic B cells from senescent mice are deficient in production of secondary isotypes (IgG1, IgG2a, IgG3, IgE), class switch recombination (CSR), and expression of the transcription factor E47. We also demonstrate that there is more Id2 (a negative regulator of E47) in old activated B cells. E47 is required for CSR, at least in part, via expression of activation-induced cytidine deaminase (AID). Our studies show that impaired induction of E47, and, subsequently, AID, contribute to poor CSR and production of secondary isotypes in senescence. We also present new data indicating the absence of DNA switch region excision circles for CSR in old activated B cells, confirming the location of the defect at the DNA endonucleolytic step. And, finally, we show that there is no change in NF-κB or Blimp-1 in old vs young stimulated B cells.
Ly-49 Receptors and Their Functions
28
10.1615/CritRevImmunol.v24.i5.20
Kevin P.
Kane
Department of Medical Microbiology and Immunology, 6-60 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
Kerry J.
Lavender
Department of Medical Microbiology and Immunology, 6-60 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
Brian J.
Ma
Department of Medical Microbiology and Immunology, 6-60 Heritage Medical Research Centre, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2
Ly-49 receptors are lectin-like type II transmembrane disulfide-bonded homodimers expressed on natural killer (NK) cells and some T-cell subsets. Cell-mediated cytotoxicity and release of cytokines/chemokines are functions regulated by Ly-49 recognition of class I major histocompatibility complex proteins (MHC-I) or virus-encoded MHC-like product(s). Here we examine diversity and conservation found within the Ly-49 gene family and explore the importance of polymorphism in Ly-49 receptor expression, specificity, and function. Several parallels are evident between Ly-49 receptors in rodents and killer Ig-related (KIR) receptors in humans, including receptor gene amplification and diversification, expression patterns, MHC-I specificity, shared signaling, and ultimate effects on NK-cell functions. These similarities suggest that insights gained in defining Ly-49 receptor functions in small animal models could have direct relevance to existing clinical challenges where there may be opportunities to manipulate human NK cells and KIR receptors for therapeutic benefit.
Role of the D Prostanoid Receptor 1 in the Modulation of Immune and Inflammatory Responses
14
10.1615/CritRevImmunol.v24.i5.30
Francois
Trottein
Centre d'Immunologie et de Biologie Parasitaire, Institut National de la Sante et de la Recherche Medicale U547, Institut Pasteur de Lille, 59019 Lille cedex, France
Christelle
Faveeuw
Centre d'Immunologie et de Biologie Parasitaire, Institut National de la Sante et de la Recherche Medicale U547, Institut Pasteur de Lille, 59019 Lille cedex, France
Philippe
Gosset
Institut National de la Sante et dela Recherche Medicale U416, Institut Pasteur de Lille, 59019, Lille cedex, France
Veronique
Angeli
Centre d’Immunologie et de Biologie Parasitaire,Institut National de la Sante et de la Recherche Medicale U547,Institut Pasteur de Lille,59019 Lille cedex, France; Department of Gene and Cell Medicine,Mount Sinai School of Medicine,New York, NY 10029
Prostaglandins (PGs) are potent eicosanoid lipid mediators derived from phospholipase-released arachidonic acid, which are involved in numerous homeostatic biological functions and inflammation. They are generated by the sequential action of cyclooxygenase isozymes and cell-specific PG synthases. Along with their role in inflammatory responses, recent accumulating evidence strongly suggests that PGs, including PGD2, are part of a complex regulatory network that modulates the immune system. PGD2 is the major prostanoid secreted by activated mast cells and has long been implicated in allergic diseases. The aim of this review is to discuss our current understanding of the mode of action of PGD2 during Th2-mediated inflammation. We also discuss recent findings, which suggest that PGD2 exerts important effects on both immune and inflammatory responses by targeting the D prostanoid receptor 1 on dendritic cells, the most potent antigen-presenting cells.
The Impact of Extracellular Acidosis on Dendritic Cell Function
22
10.1615/CritRevImmunol.v24.i5.40
Monica Elba
Vermeulen
Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina
Romina
Gamberale
Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina
Analia Silvina
Trevani
Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina
Diego
Martinez
Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina
Ana
Ceballos
AIDS Reference National Center (CNRS), Buenos Aires University School of Medicine, Buenos Aires, Argentina
Juan
Sabatte
AIDS Reference National Center (CNRS), Buenos Aires University School of Medicine, Buenos Aires, Argentina
Mirta
Giordano
Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina
Jorge Raul
Geffner
Institute of Hematologic Research, National Academy of Medicine, Department of Microbiology, AIDS Reference National Center (CNRS), Buenos Aires University School of Medicine, Buenos Aires, Argentina
Dendritic cells (DCs) are the most efficient antigen-presenting cells. They are activated in the periphery by conserved pathogen molecules and by inflammatory mediators produced by a variety of cell types in response to danger signals. It is widely appreciated that inflammatory responses in peripheral tissues are usually associated with the development of acidic microenvironments. Surprisingly, there are relatively few studies directed to analyze the effect of extracellular acidosis on the immune response. We focus on the influence of extracellular acidosis on the function of immature DCs. The results presented here show that acidosis activates DCs. It increases the acquisition of extracellular antigens for MHC class I-restricted presentation and the ability of antigen-pulsed DCs to induce both specific CD8+ CTL and B-cell responses. These findings may have important implications to our understanding of the mechanisms through which DCs sense the presence of infection or inflammation in nonlymphoid tissues.