Reciprocal regulation of polarized cytokine production by effector B and T cells

Harris, David P.; Haynes, Laura; Sayles, Peter C.; Duso, Debra K.; Eaton, Sheri M.; Lepak, Nancy M.; Johnson, Lawrence L.; Swain, Susan L.; Lund, Frances E.

doi:10.1038/82717

Cited by 732 publications

(645 citation statements)

References 47 publications

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“…Furthermore, the representations of B-cell subsets and the serum concentrations of Ig classes were unchanged at disease onset and during most of the disease course in AireϪ/Ϫ adults compared with wild-type littermates [(3, 24) and our unpublished data]. B cells can have a variety of functions: They produce Igs, release immunomodulatory cytokines, regulate lymphoid tissue neogenesis and lymphangiogenesis, present antigen, and influence the activities of dendritic cells and T cells (25)(26)(27)(28)(29). Of these functions, the production of Igs is central to certain other autoimmune disease models, for example, transfer of self-reactive Igs triggers the immediate onset of inflammatory immunopathology in arthritis, lupus nephritis, oophoritis, pemphigus, etc.…”

Section: Discussionmentioning

confidence: 99%

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

Gavanescu

Benoist

Mathis

2008

Proc. Natl. Acad. Sci. U.S.A.

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Autoimmune regulator (Aire)-deficient mice and humans have circulating autoantibodies against a multitude of organs and multiorgan autoinflammatory infiltrates. It is not known to what extent autoantibodies or their source, B lymphocytes, are required for disease onset or progression. We show in this research that B cells must be present for Aire-deficient mice to develop fulminant infiltrates. We found no evidence that autoantibodies were directly pathogenic; rather, B cells appeared to play a critical early role in T cell priming or expansion. A therapeutic reagent directed against B cells, Rituximab, induced remission of the autoimmune disease in Aire-deficient mice, raising the hope of applying it to human patients with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).autoimmunity ͉ B lymphocytes ͉ tolerance ͉ autoantibody

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Section: Discussionmentioning

confidence: 99%

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

Gavanescu

Benoist

Mathis

2008

Proc. Natl. Acad. Sci. U.S.A.

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“…It is extremely important that more recent studies demonstrate that naõ Ève B cells differentiated themselves into polarized B cells with different cytokine profiles, following stimulation with Ag and polarized effector Th1 and Th2. Polarized B cells have been termed Be1 and Be2, respectively [26], inasmuch as, once induced, these lymphocytes regulate the level of Th1 and Th2 cells. Consequently, Be1 cells, by virtue of their production of IFN-g and presentation of specific Ag to T lymphocyte, promote the expansion of Th1 cells.…”

Section: B Lymphocytes Influence the Pattern Of Immune Responses Thromentioning

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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“…In contrast, B cells do themselves play an important role in the development and maintenance of CD4 ϩ T cell memory (16,17), induction of peripheral tolerance (18), and in regulation of Th cell polarization (19,20). Although B cells are inadequate APCs for priming naive T cells (21), they can present Ags for primed or memory T cells and thereby elicit cytokine secretion (20,22).…”

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confidence: 99%

Germinal Centers Regulate Human Th2 Development

Johansson‐Lindbom

Ingvarsson

Borrebaeck

2003

The Journal of Immunology

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In the present study we demonstrate that all CD4+ T cells in human tonsil expressing the Th2-selective receptor chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) also 1) express high levels of CXCR5, and 2) display a transitional CD45RA/RO phenotype and consistently do not produce significant amounts of cytokines when immediately analyzed ex vivo. Hence, they represent precursors of Th2 effector cells, a conclusion confirmed by their robust production of IL-4, IL-5, and IL-13, but not IFN-γ, after in vitro activation. CD4+ T cells, which express only intermediate levels of CXCR5, instead develop into IFN-γ-producing cells under identical culture conditions, thus establishing a correlation between relative levels of CXCR5 expression and the acquired cytokine profile. Because CXCR5 is critically involved in follicular localization, the results suggest that these CRTH2+ Th2 cells preferentially develop their cytokine-producing phenotype within germinal centers (GCs), whereas extrafollicular differentiation instead promotes Th1 development. In support for this proposal, we show that T cells with an intermediate expression of CXCR5 can be forced to also produce IL-4 and IL-13 if cultured with allogenic GC B cells. Finally, we demonstrate that the previously described CD57+ GC T cells also express high levels of CXCR5 but instead of comprising a Th2 precursor, they represent anergized T cells. Taken together, these data suggest that GCs and B cells regulate CD4+ T cell differentiation in a finely tuned fashion, either by promoting differentiation of Th2 cells, which apparently leave the lymphoid tissue before evolving a cytokine-producing phenotype, or by furnishing T cell unresponsiveness.

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Reciprocal regulation of polarized cytokine production by effector B and T cells

Cited by 732 publications

References 47 publications

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

B cells are required for Aire-deficient mice to develop multi-organ autoinflammation: A therapeutic approach for APECED patients

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

Germinal Centers Regulate Human Th2 Development

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