Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen‐presenting activity in the development of murine lupus

Sato, Taku; Ishikawa, Sho; Akadegawa, Kenji; Ito, Toshihiro; Yurino, Hideaki; Kitabatake, Masahiro; Yoneyama, Hiroyuki; Matsushima, Kouji

doi:10.1002/eji.200425373

Cited by 69 publications

(70 citation statements)

References 26 publications

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“…1A, B), in keeping with previous work [17]. The same hierarchy of APC function was also observed in mixed lymphocyte reactions (MLR) ( [15] and Zhong, unpublished data). These results demonstrate that B1 and B2 cells manifest distinctly different antigen presentation capacity in terms of inducing T cell proliferation and cytokine secretion.…”

Section: Resultssupporting

confidence: 87%

“…B1 cells are known for the production of protective natural antibody [13,14]. B1 cell-derived immunoglobulin and B1 cells themselves, possibly through potent antigen presentation, may play a role in autoimmunity [15]. We here report that B1 and B2 cells reciprocally induce Th1/ Th17 and iT reg cells in accordance with antigen presentation capacity.…”

Section: Introductionmentioning

confidence: 63%

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Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

et al. 2007

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Regulatory T (T reg ) cells are indispensable for maintaining peripheral tolerance, whereas T helper (Th)1 and Th17 cells induce inflammation and tissue destruction. Using Foxp3-GFP knock-in mice, we report a novel regulatory role for B cell subsets in influencing the differentiation of T reg versus Th1/Th17 cells. Peritoneal B1 cells strongly promoted T cell proliferation and cytokine secretion when presenting nominal or allogeneic antigens, as compared to conventional follicular B (B2) cells. However, peritoneal B1 cells largely failed to convert naive Foxp3 -CD4 + T cells into Foxp3 + T reg cells in the presence of TGF-b and IL-2, in marked contrast to conventional B2 cells, which excelled in T reg conversion. Interestingly, under the same T reg conversion conditions, peritoneal B1 cells preferentially promoted Th1 and Th17 cell differentiation. Blockade of CD86 but not CD80 costimulation markedly enhanced T reg cell induction by B1 cells. Thus, B cell antigen presentation function is inversely correlated with de novo T reg cell induction for these B cell subsets. Our findings suggest that B1 and B2 cell subsets play distinct roles in immune regulation by promoting reciprocal differentiation of T cell lineages.

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Section: Resultssupporting

confidence: 87%

Section: Introductionmentioning

confidence: 63%

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

et al. 2007

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“…Similar findings have been reported for autoimmune prone MRL lpr/lpr and (NZB 3 NZW) F1 mice (9,22,23). Paradoxically, some clinical studies indicate abnormalities in Tregs in SLE that include increased Foxp3 + cells (24,25).…”

supporting

confidence: 87%

A Role for Intrathymic B Cells in the Generation of Natural Regulatory T Cells

Walters

Webster

Daley

et al. 2014

The Journal of Immunology

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B cells inhabit the normal human thymus, suggesting a role in T cell selection. In this study, we report that B cells can modulate thymic production of CD4+ Foxp3+ T cells (regulatory T cells [Tregs]). Mice with transgenic expression of BAFF (BAFF-Tg) harbor increased numbers of Helios+Foxp3+ thymic Tregs and, similar to some human autoimmune conditions, also exhibit increased numbers of B cells colonizing the thymus. Distinct intrathymic B cell subpopulations were identified, namely B220+, IgM+, CD23hi, CD21int cells; B220+, IgM+, CD23lo, CD21lo cells; and a population of B220+, IgM+, CD23lo, CD21hi cells. Anatomically, CD19+ B cells accumulated in the thymic medulla region juxtaposed to Foxp3+ T cells. These intrathymic B cells engender Tregs. Indeed, thymic Treg development was diminished in both B cell–deficient BAFF-Tg chimeras, but also B cell–deficient wild-type chimeras. B cell Ag capture and presentation are critical in vivo events for Treg development. In the absence of B cell surface MHC class II expression, thymic expansion of BAFF-Tg Tregs was lost. Further to this, expansion of Tregs did not occur in BAFF-Tg/Ig hen egg lysozyme BCR chimeras, demonstrating a requirement for Ag specificity. Thus, we present a mechanism whereby intrathymic B cells, through the provision of cognate help, contribute to the shaping of the Treg repertoire.

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“…Interestingly, the enlargement of thymic PVS was reported in a few other autoimmune disorders such as myasthenia gravis in humans (24) and in BWF 1 mice, a murine model for systemic lupus erythematosus (25). In these mice, B1 cells migrate aberrantly in the thymus during the development of lupus nephritis and their intra-PVS accumulation was correlated with the altered expression of the chemokine CXCL13 and adhesion molecules.…”

Section: Discussionmentioning

confidence: 91%

Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus

Mendes-da-Cruz

Smaniotto

Keller

et al. 2008

The Journal of Immunology

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We previously described a fibronectin/VLA-5-dependent impairment of NOD thymocyte migration, correlated with partial thymocyte arrest within thymic perivascular spaces. Yet, NOD thymocytes still emigrate, suggesting the involvement of other cell migration-related alterations. In this context, the aim of this work was to study the role of extracellular matrix ligands, alone or in combination with the chemokine CXCL12, in NOD thymocyte migration. Intrathymic contents of CXCL12, fibronectin, and laminin were evaluated by immunohistochemistry while the expression of corresponding receptors was ascertained by flow cytometry. Thymocyte migration was measured using Transwell chambers and transendothelial migration was evaluated in the same system, but using an endothelial cell monolayer within the chambers. NOD thymocytes express much lower VLA-5 than C57BL/6 thymocytes. This defect was particularly severe in CD4+ thymocytes expressing Foxp3, thus in keeping with the arrest of Foxp3+ cells within the NOD giant perivascular spaces. We observed an enhancement in CXCL12, laminin, and fibronectin deposition and colocalization in the NOD thymus. Furthermore, we detected altered expression of the CXCL12 receptor CXCR4 and the laminin receptor VLA-6, as well as enhanced migratory capacity of NOD thymocytes toward these molecules, combined or alone. Moreover, transendothelial migration of NOD thymocytes was diminished in the presence of exogenous fibronectin. Our data unravel the existence of multiple cell migration-related abnormalities in NOD thymocytes, comprising both down- and up-regulation of specific responses. Although remaining to be experimentally demonstrated, these events may have consequences on the appearance of autoimmunity in NOD mice.

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Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen‐presenting activity in the development of murine lupus

Cited by 69 publications

References 26 publications

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

A Role for Intrathymic B Cells in the Generation of Natural Regulatory T Cells

Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus

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Aberrant B1 cell migration into the thymus results in activation of CD4 T cells through its potent antigen‐presenting activity in the development of murine lupus

Cited by 69 publications

References 26 publications

Reciprocal generation of Th1/Th17 and Treg cells by B1 and B2 B cells

Reciprocal generation of Th1/Th17 and Treg cells by B1 and B2 B cells

A Role for Intrathymic B Cells in the Generation of Natural Regulatory T Cells

Multivectorial Abnormal Cell Migration in the NOD Mouse Thymus

Contact Info

Product

Resources

About

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells

Reciprocal generation of Th1/Th17 and T_reg cells by B1 and B2 B cells