B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new "speed congenic" stock of NOD.Ig mu null mice.

Serreze, David; Chapman, Harold D.; Varnum, Don S.; Hanson, Matthew S.; Reifsnyder, Peter C.; Richard, Scott D.; Fleming, Sara; Leiter, Edward H.; Shultz, Leonard D.

doi:10.1084/jem.184.5.2049

Cited by 536 publications

(441 citation statements)

References 20 publications

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“…The authors favour the explanation that the B cells act as APCs to autoreactive T cells rather than contribute directly to pathogenesis perhaps through cytokine production. The nonobese diabetic (NOD) mouse model of diabetes ± an organ-specific autoimmune disease also needs B cells where it is thought they play a role in Ag presentation [58,59].…”

Section: B Cells Are Required For the Initiation Of Many Autoimmune Dmentioning

confidence: 99%

Recent Progress in the Understanding of B‐Cell Functions in Autoimmunity

Porakishvili

Mageed

Jamin³

et al. 2001

Scand J Immunol

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54:30±38Our early concepts of the normal role of B cells in immunity focused on their ability to produce antibodies (Ab) and in the case of autoimmune diseases autoAbs, some of which were pathogenic. Over the past 10 years, it has became apparent that B cells display a variety of characteristics, other than Ab production, which could contribute to autoimmunity. They normally play a role in the development of lymphoid architecture, regulating T-cell subsets and dendritic cell (DC) function through cytokine production, and in activation of T cells. Receptors editing is also important in B cells which aids in immunity to infection and, possibly, prevention of autoimmunity. Transgenic animal models have now shown that B cells are necessary for many autoimmune diseases although their Ab products are not required in some cases. Negative signalling by CD5 and other molecules, such as CD22, in maintaining tolerance through recruitment of src-homology two domaincontaining protein tyrosine phosphatase-1 has also been documented. In fact, we have now reached a new era whereby the B cell has returned as an important contributor to autoimmune disorders, so that the race is on to characterize signalling regulation via the B-cell receptor and coreceptors. Identification of such molecules and their potential defects should lead to effective ways of controlling the immune response and in particular preventing the development of autoimmune states. The classical view of B cells in the biology of immune responses to infectious and self-antigens (Ag) that they promote immunity primarily by producing Ab turns out to be rather naõ Ève. Indeed, studies over the last few years indicate that this view is far from complete, and suggest that B lymphocytes have extraordinarily diverse functions within the immune system. Furthermore, it is becoming increasingly clear that the pathogenesis of autoimmune diseases cannot solely be accounted for by T cells, and intrinsic abnormalities of B cells have been described in such conditions. In this brief review we highlight some recent observations in the context of B lymphocyte in pathophysiology, and focus on their revival as pivotal players the pathophysiology in autoimmune diseases. Yet, it remains difficult to provide a model of how important B cells are in immunity and autoimmunity.

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Section: B Cells Are Required For the Initiation Of Many Autoimmune Dmentioning

confidence: 99%

Recent Progress in the Understanding of B‐Cell Functions in Autoimmunity

Porakishvili

Mageed

Jamin³

et al. 2001

Scand J Immunol

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“…Thus, the presentation of self-islet antigens to autoreactive cells is one of the critical functions underlying the outcome of disease. The priming of autoreactive T cells is carried out by antigen-presenting cells (APC) including B cells, macrophages, and DC [14,15] that are themselves responsive to growth factors such as granulocyte-monocyte colony-stimulating factor (GM-CSF).…”

Section: Introductionmentioning

confidence: 99%

Increased islet antigen presentation leads to type‐1 diabetes in mice with autoimmune susceptibility

et al. 2004

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Granulocyte-macrophage colony-stimulating factor (GM-CSF) is frequently used in preclinical and clinical protocols to modulate autoimmune responses, bone marrow transplants, and recovery from immune ablative therapies. The immunological outcome of such therapies is not fully understood. We tested the hypothesis that GM-CSF would enhance the maturation of antigen-presenting cells, facilitating presentation of g -cell autoantigens to autoreactive T cells. We found that islet expression of GM-CSF greatly enhanced disease in male mice. Islet-derived APC but not splenic APC showed markedly enhanced capacity to stimulate in vitro proliferative responses of islet-antigen-specific autoreactive T cells. In vivo transfer of CD8 + and CD4 + T cells demonstrate that autoreactive T cells undergo extensive division in pancreatic lymph nodes of GM-CSF-transgenic mice compared with wild-type NOD male mice. Together, the results presented here demonstrate that expression of GM-CSF in the pancreas can enhance autoimmunity in disease-susceptible mice.

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“…Given that B cells and CD8 ϩ T cells are also both critical for disease in graft-versus-host-disease (29,30,33) and nonobese diabetic mice (31,34,35), the indirect mechanism by which B cells promote CD8 ϩ T cell activation demonstrated in this report may reflect a general feature of alloimmune and autoimmune pathogenesis.…”

Section: Discussionmentioning

confidence: 74%

Cutting Edge: B Cells Promote CD8+ T Cell Activation in MRL-FaslprMice Independently of MHC Class I Antigen Presentation

Chan¹,

Shlomchik

2000

The Journal of Immunology

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Spontaneous CD8+ T cell activation in MRL-Faslpr mice is B cell dependent. It is unclear whether this B-dependent activation is mediated by direct Ag presentation via MHC class I proteins (i.e., cross-presentation) or whether activation occurs by an indirect mechanism, e.g., via effects on CD4+ cells. To determine how CD8+ T cell activation is promoted by B cells, we created mixed bone marrow chimeras where direct MHC class I Ag presentation by B cells was abrogated while other leukocyte compartments could express MHC class I. Surprisingly, despite the absence of B cell class I-restricted Ag presentation, CD8+ T cell activation was intact in the chimeric mice. Therefore, the spontaneous B cell-dependent CD8+ T cell activation that occurs in systemic autoimmunity is not due to direct presentation by B cells to CD8+ T cells.

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B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new "speed congenic" stock of NOD.Ig mu null mice.

Cited by 536 publications

References 20 publications

Recent Progress in the Understanding of B‐Cell Functions in Autoimmunity

Recent Progress in the Understanding of B‐Cell Functions in Autoimmunity

Increased islet antigen presentation leads to type‐1 diabetes in mice with autoimmune susceptibility

Cutting Edge: B Cells Promote CD8+ T Cell Activation in MRL-FaslprMice Independently of MHC Class I Antigen Presentation

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