CCR6-Dependent Positioning of Memory B Cells Is Essential for Their Ability To Mount a Recall Response to Antigen

Elgueta, Raúl; Marks, Ellen; Nowak, Elizabeth C.; Menezes, Shinelle; Benson, Micah J.; Raman, Vanitha S.; Ortiz, Carla; O’Connell, Samuel; Hess, Henry; Lord, Graham M.; Noelle, Randolph J.

doi:10.4049/jimmunol.1401553

Cited by 74 publications

(93 citation statements)

References 31 publications

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“…To assess whether RA signaling affects the development of B cells in the bone marrow, we quantified the percentage and absolute numbers of pre-B cells (B220 + IgM neg IgD neg ), immature B cells (B220 + IgM hi IgD neg ), and mature B cells (B220 + IgM int IgD + ) in dnRARαCD19 Cre mice, as previously described (29). Our results showed an increase in the percentage of immature B cells in dnRARαCD19 Cre mice compared with controls (Figure 4B).…”

Section: Resultsmentioning

confidence: 99%

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Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

et al. 2016

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Retinoic acid (RA) plays an important role in the balance of inflammation and tolerance in T cells. Furthermore, it has been demonstrated that RA facilitates IgA isotype switching in B cells in vivo. However, it is unclear whether RA has a direct effect on T-independent B cell responses in vivo. To address this question, we generated a mouse model where RA signaling is specifically silenced in the B cell lineage. This was achieved through the overexpression of a dominant negative receptor α for RA (dnRARα) in the B cell lineage. In this model, we found a dramatic reduction in marginal zone (MZ) B cells and accumulation of transitional 2 B cells in the spleen. We also observed a reduction in B1 B cells in the peritoneum with a defect in the T-independent B cell response against 2,4,6-trinitrophenyl. This was not a result of inhibited development of B cells in the bone marrow, but likely the result of both defective expression of S1P1 in MZ B cells and a defect in the development of MZ and B1 B cells. This suggests that RARα expression in B cells is important for B cell frequency in the MZ and peritoneum, which is crucial for the generation of T-independent humoral responses.

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Section: Resultsmentioning

confidence: 99%

“…Single-cell preparations were obtained from the spleen and the number of TNP-IgM, TNP-IgG 3 , and TNP-IgG 1 antibody-secreting cells (ASCs) were determined by ELISPOT as previously reported (29, 30). …”

Section: Methodsmentioning

confidence: 99%

Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

et al. 2016

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“…11 Production of the chemoattractants CXCL10, CXCL13, and CCL20 in the CNS has been associated with B-cell recruitment, distribution, and reactivity in MS. [24][25][26] We compared the presence of B cells that express the chemokine receptors that correspond to these ligands, CXCR3 + (CXCL10), CXCR5 + (CXCL13), and CCR6 + (CCL20), between paired blood, CSF, and meningeal and brain tissues from 10 MS patients (see Table 1). 11 Production of the chemoattractants CXCL10, CXCL13, and CCL20 in the CNS has been associated with B-cell recruitment, distribution, and reactivity in MS. [24][25][26] We compared the presence of B cells that express the chemokine receptors that correspond to these ligands, CXCR3 + (CXCL10), CXCR5 + (CXCL13), and CCR6 + (CCL20), between paired blood, CSF, and meningeal and brain tissues from 10 MS patients (see Table 1).…”

Section: Cxcr3-expressing B Cells Are Selectively Enriched In Distincmentioning

confidence: 99%

Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

Langelaar

Rijvers

Janssen

et al. 2019

Annals of Neurology

136

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Objective Results from anti‐CD20 therapies demonstrate that B‐ and T‐cell interaction is a major driver of multiple sclerosis (MS). The local presence of B‐cell follicle‐like structures and oligoclonal bands in MS patients indicates that certain B cells infiltrate the central nervous system (CNS) to mediate pathology. Which peripheral triggers underlie the development of CNS‐infiltrating B cells is not fully understood. Methods Ex vivo flow cytometry was used to assess chemokine receptor profiles of B cells in blood, cerebrospinal fluid, meningeal, and brain tissues of MS patients (n = 10). Similar analyses were performed for distinct memory subsets in the blood of untreated and natalizumab‐treated MS patients (n = 38). To assess T‐bet(CXCR3)+ B‐cell differentiation, we cultured B cells from MS patients (n = 21) and healthy individuals (n = 34) under T helper 1‐ and TLR9‐inducing conditions. Their CNS transmigration capacity was confirmed using brain endothelial monolayers. Results CXC chemokine receptor 3 (CXCR3)‐expressing B cells were enriched in different CNS compartments of MS patients. Treatment with the clinically effective drug natalizumab prevented the recruitment of CXCR3high IgG1+ subsets, corresponding to their increased ability to cross CNS barriers in vitro. Blocking of interferon‐γ (IFNγ) reduced the transmigration potential and antigen‐presenting function of these cells. IFNγ‐induced B cells from MS patients showed increased T‐bet expression and plasmablast development. Additional TLR9 triggering further upregulated T‐bet and CXCR3, and was essential for IgG1 switching. Interpretation This study demonstrates that T‐bethigh IgG1+ B cells are triggered by IFNγ and TLR9 signals, likely contributing to enhanced CXCR3‐mediated recruitment and local reactivity in the CNS of MS patients. ANN NEUROL 2019;86:264–278

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“…Using these models, we analyzed the proportion of immature B cells (B220 + IgM hi IgD + ), mature B cells (B220 + IgM int IgD + ) and pre-B cells (B220 + IgM + IgD + ) from bone marrow (53, 54). However, no changes were detected in B cell subsets in the bone marrow of Plvap iECKO mice as compared to controls or Plvap iECRC mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

Endothelial Plasmalemma Vesicle–Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells

Elgueta

Tse

Deharvengt

et al. 2016

The Journal of Immunology

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Plasmalemma vesicle associated protein (Plvap) is an endothelial protein with roles in endothelial diaphragm formation and maintenance of basal vascular permeability. At the same time Plvap has roles in immunity by facilitating leukocyte diapedesis at inflammatory sites and controlling peripheral lymph node morphogenesis and the entry of soluble antigens into lymph node conduits. Based on its postulated role in diapedesis, we have investigated the role of Plvap in hematopoiesis and show that deletion of Plvap results in a dramatic decrease of IgM+IgDlo B cells in both the spleen and peritoneal cavity. Tissue specific deletion of Plvap demonstrates that the defect is B cell extrinsic, as B cell and pan hematopoietic Plvap deletion has no effect on IgM+IgDlo B cell numbers. Endothelial specific deletion of Plvap in the embryo or at adult stage recapitulates the full Plvap knockout phenotype whereas endothelial specific reconstitution of Plvap under the Chd5 promoter rescues the IgM+IgDlo B cell phenotype. Taken together, these results show that Plvap expression in endothelial cells is important in the maintenance of IgM+ B cells in the spleen and peritoneal cavity.

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CCR6-Dependent Positioning of Memory B Cells Is Essential for Their Ability To Mount a Recall Response to Antigen

Cited by 74 publications

References 31 publications

Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

Retinoic Acid Signaling in B Cells Is Required for the Generation of an Effective T-Independent Immune Response

Induction of brain‐infiltrating T‐bet–expressing B cells in multiple sclerosis

Endothelial Plasmalemma Vesicle–Associated Protein Regulates the Homeostasis of Splenic Immature B Cells and B-1 B Cells

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