Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis

Carnrot, Cecilia; Prokopec, Kajsa E.; Råsbo, Kristina; Karlsson, Mikael C. I.; Kleinau, Sandra

doi:10.1038/cmi.2011.2

Cited by 30 publications

(35 citation statements)

References 45 publications

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“…13 In this article, we report the analysis of the autoimmune response to autologous CII in MZ B cells and by what mechanisms these cells may contribute to autoimmune arthritis and how they are regulated.…”

Section: Discussionmentioning

confidence: 99%

“…Any possible contamination of transitional B cells or CD5 1 cells was considered negligible using this sorting protocol. 13 For sorting of B-1 and MZ B cells, the splenocytes were labeled with fluorochrome-conjugated anti-mouse CD1d (clone 1B1; Biolegend) and anti-mouse B220 (clone RA3-6B2; Biolegend) together with biotinylated anti-mouse CD43 (clone eBioR2/60; eBioscience, San Diego, CA, USA) followed by fluorochrome-conjugated streptavidin (Biolegend), both steps at 4 uC for 30 minutes followed by washing. The cells were subsequently sorted into B-1 and MZ B cells using a BD FACSAriaIII and FACSDiva software v. 6.1.3 (BD Biosciences).…”

Section: Preparation Of Cellsmentioning

confidence: 99%

“…We have previously demonstrated that MZ B cells are naturally reactive to heterologous CII and expand rapidly following immunization with this antigen for induction of CIA. 13 The MZ B cells are distinguishable from the more common follicular (FO) B cells by their anatomical distribution in the splenic MZ of follicles and their high expression of IgM, CR1/2, FccRIIb, and CD1d. [13][14][15] They quickly mount immune responses to type I and type II thymus-independent antigens, inducing extensive BCR crosslinking and co-engagement of multiple pattern recognition receptors including toll-like receptors (TLRs), which enables them to quickly respond with IgM production in a first line of defense.…”

Section: Introductionmentioning

confidence: 99%

“…13 The MZ B cells are distinguishable from the more common follicular (FO) B cells by their anatomical distribution in the splenic MZ of follicles and their high expression of IgM, CR1/2, FccRIIb, and CD1d. [13][14][15] They quickly mount immune responses to type I and type II thymus-independent antigens, inducing extensive BCR crosslinking and co-engagement of multiple pattern recognition receptors including toll-like receptors (TLRs), which enables them to quickly respond with IgM production in a first line of defense. [16][17][18][19][20] Furthermore, owing to their pre-activated state and high surface expression class II MHC (MHCII), CD80 and CD86, the MZ B cells represent powerful activators of CD4 1 T cells.…”

Section: Introductionmentioning

confidence: 99%

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Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

et al. 2015

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Polyreactive innate-type B cells account for many B cells expressing self-reactivity in the periphery. Improper regulation of these B cells may be an important factor that underlies autoimmune disease. Here we have explored the influence of self-reactive innate B cells in the development of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis. We show that splenic marginal zone (MZ), but not B-1 B cells exhibit spontaneous IgM reactivity to autologous collagen II in naïve mice. Upon immunization with heterologous collagen II in complete Freund's adjuvant the collagen-reactive MZ B cells expanded rapidly, while the B-1 B cells showed a modest anti-collagen response. The MZ B cells were easily activated by toll-like receptor (TLR) 4 and 9-ligands in vitro, inducing proliferation and cytokine secretion, implying that dual engagement of the B-cell receptor and TLRs may promote the immune response to self-antigen. Furthermore, collagen-primed MZ B cells showed significant antigen-presenting capacity as reflected by cognate T-cell proliferation in vitro and induction of IgG anti-collagen antibodies in vivo. MZ B cells that were deficient in complement receptors 1 and 2 demonstrated increased proliferation and cytokine production, while Fcc receptor IIb deficiency of the cells lead to increased cytokine production and antigen presentation. In conclusion, our data highlight self-reactive MZ B cells as initiators of the autoimmune response in CIA, where complement and Fc receptors are relevant in controlling the self-reactivity in the cells.

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Section: Discussionmentioning

confidence: 99%

Section: Preparation Of Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

et al. 2015

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“…20 Culture supernatants and mouse serum levels of IL-17, transforming growth factor-beta (TGF-b), IFN-c, and IL-10 were measured with ELISA Kits (eBioscience, San Diego, CA) following the manufacturer's protocol. Nitric oxide (NO) was detected by determining the concentration of nitrite that accumulated in the culture supernatants using the colorimetric Griess reaction (Promega, Madison, WI).…”

Section: Autoantibody and Cytokine Detectionmentioning

confidence: 99%

Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

et al. 2015

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MZ B cells migrate in a T‐bet dependent manner and might contribute to the remission of collagen‐induced arthritis by the secretion of IL‐10

2016

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IntroductionIn mice, marginal zone (MZ) B cells are mostly found in the outer white pulp of the spleen between the marginal sinus and the red pulp. They shuttle between MZ and follicles and transport antigens to follicles where they activate T cells and differentiate into plasma cells [1][2][3] self-renew and primarily express polyreactive BCRs, which recognize conserved molecular patterns that are often shared by foreign and autologous antigens [4][5][6]. Besides the BCRs mouse MZ B cells express high levels of TLRs including TLR9, which recognizes hypomethylated CpG motifs in bacterial DNA or in chromatin complexes expressed on the surface of apoptotic cells and bodies [7][8][9]. Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that has been used extensively for elucidating the role of individual cell types in disease onset and progression. The use of CIA as a model for RA is based on pathological similarities between the two diseases [10]. However, CIA differs from chronic RA in that the inflammatory phase is usually of limited . CIA is mostly considered as a Th1-mediated autoimmune disease. Differentiation of Th1 cells is crucially dependent on the expression of the transcription factor T-bet (T-box transcription factor), which is induced by the IFN-γ signaling pathways [13]. Beyond its well-known role in Th1 cells, T-bet has an important impact on B-cell functions. Experiments using T-bet-deficient, lupus-prone mice showed that T-bet is required for the induction of IgG2a germ-line transcripts by IFN-γ and suggested that it regulates IgG2a class-switching in a B-cell intrinsic way [14]. B-cell intrinsic T-bet expression was also found in ageassociated B cells, a recently discovered B-cell subset with a unique surface phenotype that arise prematurely in autoimmune-prone mouse strains or accumulates progressively with age and prone to IgG2a/c production [15]. Moreover, it was recently demonstrated that in mature B cells the signaling cascades driven by the BCR and TLR9 converged at the level of T-bet and acted synergistically on it [16]. Considered all these observations on T-bet and the functional plasticity of MZ B cells with their confirmed but not entirely clear role in arthritis prompted us to examine the involvement of MZ B cells in the regulation of CIA particularly focusing on T-bet involvement.Our results clearly demonstrate that MZ B cells express an elevated level of T-bet in the remission phase of CIA. We confirmed the existence of an IL-10 producing, T-bet positive subpopulation of MZ B cells. Furthermore showed that T-bet positive MZ B cells are able to migrate toward ligand interacting with T-bet regulated CXCR3 and robustly secrete IL-10 in response to inflammatory stimuli. These data suggest that T-bet might contribute to the downregulation of CIA by promoting the regulatory capacity of IL-10 producing MZ B cells. Results and discussionMZ B cells express elevated levels of T-bet in the remission phase of CIA Autoimmune diseases related to Th1 immunity require T...

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Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis

Cited by 30 publications

References 45 publications

Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

Function and regulation of self-reactive marginal zone B cells in autoimmune arthritis

Olfactory ecto-mesenchymal stem cells possess immunoregulatory function and suppress autoimmune arthritis

MZ B cells migrate in a T‐bet dependent manner and might contribute to the remission of collagen‐induced arthritis by the secretion of IL‐10

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