The Sequential Role of Lymphotoxin and B Cells in the Development of Splenic Follicles

González, Mercedes Freire; Mackay, Fabienne; Browning, Jeffrey L.; Kosco‐Vilbois, Marie H.; Noelle, Randolph J.

doi:10.1084/jem.187.7.997

Cited by 208 publications

(167 citation statements)

References 30 publications

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“…The positive regulatory roles of B cells extend to multiple immune system components; the absence of B cells during mouse development results in significant quantitative and qualitative abnormalities within the immune system, including a remarkable decrease in thymocyte numbers and diversity [12], significant defects within spleen dendritic cell and T cell compartments [13-15], absence of Peyer's patch organogenesis and follicular dendritic cell networks [16,17], and absence of marginal zone and metallophilic macrophages with decreased chemokine expression [15,17]. B cells also positively regulate lymphoid tissue organization [18,19]. Finally, dendritic cell, macrophage, and T H cell development may all be influenced by B cells during the formation of immune responses [20].…”

Section: Introductionmentioning

confidence: 99%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

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B cell abnormalities contribute to the development and progress of autoimmune disease. Traditionally, the role of B cells in autoimmune disease was thought to be predominantly limited to the production of autoantibodies. Nevertheless, in addition to autoantibody production, B cells have other functions potentially relevant to autoimmunity. Such functions include antigen presentation to and activation of T cells, expression of co-stimulatory molecules and cytokine production. Recently, the ability of B cells to negatively regulate cellular immune responses and inflammation has been described and the concept of regulatory B cells has emerged. A variety of cytokines produced by regulatory B cell subsets have been reported, with IL-10 being the most studied. In this review, this specific IL-10-producing subset of regulatory B cells has been labeled B10 cells to highlight that the regulatory function of these rare B cells is mediated by IL-10, and to distinguish them from other B cell subsets that regulate immune responses through different mechanisms. B10 cells are a functionally defined subset currently identified only by their competency to produce and secrete IL-10 following appropriate stimulation. Although B10 cells share surface markers with other previously defined B cell subsets, currently there is no cell surface or intracellular phenotypic marker or set of markers unique to B10 cells. The recent discovery of an effective way to expand B10 cells ex vivo opens new horizons in the potential therapeutic applications of this rare B cell subset. This review highlights the current knowledge on B10 cells and discusses their potential as novel therapeutic agents in autoimmunity.

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Section: Introductionmentioning

confidence: 99%

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

2013

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“…In SCID mice, which lack FDC as a result of the absence of mature B cells (29), the differentiation of FDC precursors into mature FDC can be induced within a few days after adoptive B cell transfer (30 -32). This induction is dependent on LT␣/LT␤R signaling by B cells, since it is not elicited by transfer of LT␣ Ϫ/Ϫ B cells (32). Thus, B cells from 1-wk-old naive BALB/c mice were tested for their capacity to generate FDC differentiation following their i.v.…”

Section: Neonatal B Cell-mediated Signaling To Fdc Precursorsmentioning

confidence: 99%

Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens

Pihlgren

Tougne

Bozzotti

et al. 2003

The Journal of Immunology

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The factors limiting neonatal and infant IgG Ab responses to T-dependent Ags are only partly known. In this study, we assess how these B cell responses are influenced by the postnatal development of the spleen and lymph node microarchitecture. When BALB/c mice were immunized with alum-adsorbed tetanus toxoid at various stages of their immune development, a major functional maturation step for induction of serum IgG, Ab-secreting cells, and germinal center (GC) responses was identified between the second and the third week of life. This correlated with the development of the follicular dendritic cell (FDC) network, as mature FDC clusters only appeared at 2 wk of age. Adoptive transfer of neonatal splenocytes into adult SCID mice rapidly induced B cell follicles and FDC precursor differentiation into mature FDC, indicating effective recruitment and signaling capacity of neonatal B cells. In contrast, adoptive transfer of adult splenocytes into neonatal SCID mice induced primary B cell follicles without any differentiation of mature FDC and failed to correct limitations of tetanus toxoid-induced GC. Thus, unresponsiveness to lymphoid-mediated signals at the level of neonatal FDC precursors delays FDC maturation and GC induction, thus limiting primary Ab-secreting cell responses to T-dependent Ags in early postnatal life.

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“…Subsequent studies established that host-derived DCs differentiate in the spleen of SCID mice after transfer of wild-type lymphocytes [8±10]. The recent elegant studies by Gonzalez et al [11] are even more relevant to the role of B lymphocytes in that they showed that B cells induce the appearance of DCs through the expression of membrane LT-a. These investigators observed that, following the transfer of B cells from membrane LT-a 1/1 but not LT-a 2/± , the expression of LT-a/2b on B lymphocytes, but not T lymphocytes, was critical for the formation of DC nettings.…”

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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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The Sequential Role of Lymphotoxin and B Cells in the Development of Splenic Follicles

Cited by 208 publications

References 30 publications

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

IL-10-producing regulatory B cells (B10 cells) in autoimmune disease

Unresponsiveness to Lymphoid-Mediated Signals at the Neonatal Follicular Dendritic Cell Precursor Level Contributes to Delayed Germinal Center Induction and Limitations of Neonatal Antibody Responses to T-Dependent Antigens

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

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