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1

B cell development and primary immunodeficiencies with hypogammaglobulinemia

100%

Hokibara S., Agematsu K., Komiyama A.

Archivum Immunologiae et Therapiae Experimentalis

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2000

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vol. 48

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issue 4

267-271

EN

The differentiation of B cells along the pathway of B cell development has been well characterized. In the bone marrow, the differentiation from pro-B cells to immature B cells can be defined by several surface antigens, such as a surrogate light chain. Immature B cells become mature B cells and then circulate in the peripheral blood as naive B cells. In the peripheral lymphoid tissues, naive B cells differentiate into memory B cells, which express the CD27 molecule, or plasma cells. Primary immunodeficiencies with hypogammaglobulinemia are caused by defects of the specific molecules which are needed for the B cell differentiation. Recent studies of the genes responsible for such immunodeficiencies have clarified B cell development as well as their pathogenesis. We discuss here the molecules affecting the B cell development and primary immunodeficiencies with hypogammaglobulinemia.

2

Manipulating B cell homeostasis: a key component in the advancement of targeted strategies

100%

Treml L. S., Quinn I. W. J., Treml J. M., Scholz J. L., Cancro M. P.

Archivum Immunologiae et Therapiae Experimentalis

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2008

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vol. 56

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issue 3

153-164

EN

Understanding the homeostatic mechanisms governing lymphocyte pools achieves critical importance as lymphocyte-targeted therapies expand in use and scope. The primacy of B lymphocyte stimulator (BLyS) family ligands and receptors in governing B lymphocyte homeostasis has become increasingly clear in recent years, affording insight into novel opportunities and potential pitfalls for targeted B cell therapeutics. Interclonal competition for BLyS-BR3 interactions determines the size of na?ve B cell pools and can regulate the stringency of selection applied as cells complete maturation. Thus one of the predicted consequences of ablative therapies targeting primary pools is relaxed negative selection. This suggests that BLyS levels and B cell reconstitution rates may serve useful prognostic roles and that BLyS itself might be targeted to circumvent relapse. Alternatively, manipulations that allow rare, minimally autoreactive specificities to survive and mature may lead to opportunities in cases where antibody-based vaccine development has heretofore been unsuccessful. BLyS family ligands and receptors also play a role in activated and memory B cell pools, suggesting they might likewise be targeted to promote or delete particular antigen-experienced subpopulations in a similar way.

3

Molecular mechanisms of CD40 signaling

100%

Bishop G. A., Hostager B. S.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 2

129-138

EN

CD40, a member of the growing tumor necrosis factor receptor (TNF-R) family of molecules, functions as a transmembrane signal receptor in both hematopoietic and non-hematopoietic cell types, although its physiological roles are less well understood in the latter. Much has been learned over the past decade about the role of CD40 signaling in various cellular functions. In addition, some of the molecular events which occur subsequent to CD40 engagement have been characterized, although much remains to be understood. This review will summarize the known important biological roles of CD40, and discuss what is currently known about how CD40 signals.

4

Ligand-independent activity of the B cell antigen receptor in physiology and pathology

100%

Corcos D.

Archivum Immunologiae et Therapiae Experimentalis

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2007

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vol. 55

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issue 2

77-82

EN

The B cell receptor (BCR) is required for stimulation of B cells by antigen, and is also involved in the negative selection of autoreactive B cells. In the past few years, a constitutive ligand-independent signaling activity of the BCR has been demonstrated. In this paper, the various findings are summarized and their interpretation and their significance, both in pathology and in physiology discussed. The constitutive activity of the BCR may be important for tumor formation, at least in the case of heavy-chain diseases, neoplastic proliferations developed from B cells. A large body of evidence suggests that this activity could be required for B cell survival and would play a role in B cell development as a process monitoring BCR functionality. A model explaining signaling in the absence of antigen as a function of dimer formation is proposed. The putative constitutive activity of the pre-BCR is also discussed.

5

Immunoglobulin repertoire of rearranged VH segments in human blood

100%

Kraj P.

Postępy Higieny i Medycyny Doświadczalnej

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1995

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vol. 49

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issue 1

9-22

6

Deconstructing B cell tolerance to basement membranes

88%

Foster M. H., Zhang Y., Clark A. G.

Archivum Immunologiae et Therapiae Experimentalis

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2006

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vol. 54

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issue 4

227-237

EN

Basement membrane antigens are frequent targets of autoantibody attack in systemic and organ-restricted autoimmunity. These specialized and highly organized matrices are composed of multiple components with restricted tissue distributions and limited epitope exposure. To the dissect mechanisms controlling humoral autoimmunity to nephritogenic basement membrane antigens, we developed autoantibody transgenic models. In mice bearing the LamH Ig transgene encoding B cell receptors specific for laminin, autoreactive B cells are readily generated but actively regulated in vivo. In this model, anti-laminin B cells are immunologically censored by mechanisms that include central deletion, k light-chain editing, and anergy. Tolerance is maintained when the transgene is established in MRL and BXSB genetic backgrounds with inherited autoimmune susceptibility, and despite provocation with potent environmental stimulants. Collectively, these studies indicate that the pathogenic anti-laminin reactivity characteristic of systemic lupus is tightly regulated. A novel anti-collagen transgenic model is used to assess the tolerogenesis of a structurally distinct pathogenic basement membrane epitope and to determine if the reactivity to putative cryptic epitopes targeted in organ-restricted disease is regulated. These studies should provide insight into the molecular mechanisms controlling basement membrane autoreactivity and ultimately facilitate the development of novel strategies to inactivate autoreactive cells and treat autoimmune disease.

7

Functions of human complement inhibitor C4b-binding protein in relation to its structure

75%

Blom A. M., Villoutreix B. O., Dahlback B.

Archivum Immunologiae et Therapiae Experimentalis

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2004

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vol. 52

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issue 2

83-95

EN

Considering the destructive potential of the complement cascade, it is no surprise that there are several complement inhibitors present in blood and expressed on virtually all cells of the body to protect self tissue. C4b-binding protein (C4BP) is a potent soluble inhibitor of the classical and lectin pathways of complement. This large (500 kDa) plasma glycoprotein consists of seven identical 75 kDa alpha-chains and a unique 40 kDa alpha-chain that are held together by disulphide bridges. Both types of subunit are almost exclusively composed of complement control protein (CCP) domains. In recent years, detailed studies of structure-function relationships have yielded new understanding of the interactions between C4BP and the activated complement factors C4b and C3b, heparin, and vitamin K-dependent anticoagulant protein S. This review describes the localization of binding sites for a number of C4BP ligands in relation to well-established and novel functions of C4BP such as complement inhibition, protection of apoptotic cells from complement, CD40-dependent stimulation of B cells, and the contribution of a number of human pathogens to pathogenesis.

8

The biological role and potential therapeutic application of interleukin 7

75%

Krawczenko A., Kieda C., Dus D.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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vol. 53

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issue 6

518-527

EN

Interleukin 7 (IL)-7 is a pleiotropic, non-redundant cytokine necessary for the development of B and T lymphocytes, in particular gamma delta T cell receptor-positive cell differentiation. The cytokine can function as a cofactor during myelopoiesis and the generation of cytotoxic T cells and natural killer cells, can activate monocytes/macrophages, and support the survival of mature T cells. A role for IL-7 in promoting the formation of Peyer's patch anlage has also been demonstrated. IL-7 is constitutively expressed in the thymus, bone marrow stromal cells, epithelial and dendritic cells, keratinocytes, as well as in fetal and adult liver. IL-7 acts on various cells through its receptor (IL-7R), a heterodimer consisting of an alpha chain (CD127) that specifically binds IL-7 and a common c chain (CD132) shared by other cytokine receptors. The receptor is expressed on bone marrow progenitor cells, lymphoid T and B precursors, and mature T cells. IL-7 activity towards murine endothelial cells has been recently described. The presence of IL-7R on human endothelial cells has also been demonstrated. Several therapeutic applications of recombinant IL-7 have been proposed. These have focused on the enhancement of lymphopoiesis, promotion of stem cell engraftment, and the anti-tumor activity of the cytokine.

9

Preventing staphylococcal disease by disarming the immune responses to infection

75%

Tarkowski A.

Archivum Immunologiae et Therapiae Experimentalis

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2000

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vol. 48

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issue 1

21-26

EN

Use of experimental models of staphylococcal infections clarified several bacterial virulence factors as well as many hematopoetic cell types and their products that are involved in the pathogenesis of infection. For many decades it has been believed that antibody mediated response to staphylococci and their products was the major, if not the only one, hallmark of immune reactivity during infection. Recent studies have documented that T cell mediated responses to superantigens produced by staphylococci are not only prominent but also decisive with respect to sequels. Also the nonantigen specific immune responsiveness to staphylococcal infection is reviewed including roles of neutrophils, complement system and nitric oxide. The knowledge gained regarding staphylococcal virulence factors and the host immune responses has prompted researchers to develop new strategies how to interact in vivo witl the infectious process. Some of these approaches are commented in this review regarding e. g. vaccination procedures in order to prevent severe infections as well as therapeutic procedures to minimize organ damage during an ongoing infectious process.

Refine search results

B cell development and primary immunodeficiencies with hypogammaglobulinemia

Manipulating B cell homeostasis: a key component in the advancement of targeted strategies

Molecular mechanisms of CD40 signaling

Ligand-independent activity of the B cell antigen receptor in physiology and pathology

Immunoglobulin repertoire of rearranged VH segments in human blood

Deconstructing B cell tolerance to basement membranes

Functions of human complement inhibitor C4b-binding protein in relation to its structure

The biological role and potential therapeutic application of interleukin 7

Preventing staphylococcal disease by disarming the immune responses to infection