Yolande Richard | Université Paris Descartes (original) (raw)

Papers by Yolande Richard

Viruses, 2021

B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendr... more B-cell follicles constitute large reservoirs of infectious HIV/SIV associated to follicular dendritic cells and infecting follicular helper (TFH) and regulatory (TFR) T-cells in germinal centers (GCs). Thus, follicular and GC B-cells are persistently exposed to viral antigens. Despite recent development of potent HIV immunogens, numerous questions are still open regarding GC reaction during early HIV/SIV infection. Here, we dissect the dynamics of B- and T-cells in GCs of macaques acutely infected by SIV (Group SIV+) or vaccinated with Tetanus Toxoid (Group TT), a T-dependent model antigen. Systemic inflammation and mobilization of antigen-presenting cells in inguinal lymph nodes and spleen are lower in Group TT than in Group SIV+. Despite spleen GC reaction of higher magnitude in Group SIV+, the development of protective immunity could be limited by abnormal helper functions of TFH massively polarized into TFH1-like cells, by inflammation-induced recruitment of fCD8 (either regulat...

Journal of Visualized Experiments, 2020

Studying isolated cells from mucosa-associated lymphoid tissues (MALT) allows understanding of im... more Studying isolated cells from mucosa-associated lymphoid tissues (MALT) allows understanding of immune cells response in pathologies involving mucosal immunity, because they can model host-pathogen interactions in the tissue. While isolated cells derived from tissues were the first cell culture model, their use has been neglected because tissue can be hard to obtain. In the present protocol, we explain how to easily process and culture tonsillar mononuclear cells (TMCs) from healthy human tonsils to study innate immune responses upon activation, mimicking viral infection in mucosal tissues. Isolation of TMCs from the tonsils is quick, because the tonsils barely have any epithelium and yield up to billions of all major immune cell types. This method allows detection of cytokine production using several techniques, including immunoassays, qPCR, microscopy, flow cytometry, etc., similar to the use of peripheral mononuclear cells (PBMCs) from blood. Furthermore, TMCs show a higher sensitivity to drug testing than PBMCs, which needs to be considered for future toxicity assays. Thus, ex vivo TMCs cultures are an easy and accessible mucosal model.

International journal of molecular sciences, Jan 3, 2014

The CD40 ligand (CD40L) is a transmembrane molecule of crucial interest in cell signaling in inna... more The CD40 ligand (CD40L) is a transmembrane molecule of crucial interest in cell signaling in innate and adaptive immunity. It is expressed by a variety of cells, but mainly by activated T-lymphocytes and platelets. CD40L may be cleaved into a soluble form (sCD40L) that has a cytokine-like activity. Both forms bind to several receptors, including CD40. This interaction is necessary for the antigen specific immune response. Furthermore, CD40L and sCD40L are involved in inflammation and a panoply of immune related and vascular pathologies. Soluble CD40L is primarily produced by platelets after activation, degranulation and cleavage, which may present a problem for transfusion. Soluble CD40L is involved in adverse transfusion events including transfusion related acute lung injury (TRALI). Although platelet storage designed for transfusion occurs in sterile conditions, platelets are activated and release sCD40L without known agonists. Recently, proteomic studies identified signaling path...

Retrovirology, 2012

Background Conflicting results regarding changes in mucosal IgA production or in the proportions ... more Background Conflicting results regarding changes in mucosal IgA production or in the proportions of IgA plasma cells in the small and large intestines during HIV-infection have been previously reported. Except in individuals repeatedly exposed to HIV-1 but yet remaining uninfected, HIV-specific IgAs are frequently absent in mucosal secretions from HIV-infected patients. However, little is known about the organization and functionality of mucosal B-cell follicles in acute HIV/SIV infection during which a T-dependent IgA response should have been initiated. In the present study, we evaluated changes in B-cell and T-cell subsets as well as the extent of apoptosis and class-specific plasma cells in Peyer’s Patches, isolated lymphoid follicles, and lamina propria. Plasma levels of IgA, BAFF and APRIL were also determined. Results Plasma IgA level was reduced by 46% by 28 days post infection (dpi), and no IgA plasma cells were found within germinal centers of Peyer’s Patches and isolated ...

Leukemia Research, 1982

A~traet-Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in norm... more A~traet-Adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) were measured in normal human and in malignant lymphoid cells. Thymocytes had high ADA activity (21.2 +__ 6.8 103 nM/h/mg) and low PNP activity (1.2 _ 0.6), whereas T peripheral blood lymphocytes (PBL) had low ADA activity (1.20 + 0.22) and high PNP activity (2.8 + 1.3). Moreover cortico-thymocytes had higher ADA and lower PNP levels than medullary thymocytes. A linear correlation was observed between ADA and PNP activities in both thymocytes and T-PBL. Cells from 13 patients with T acute lymphoblastic leukemia (ALL) and 10 patients with T lymphoblastic lymphoma (LL) had very high levels of ADA (respectively 13.0 + 5.4 and 22.8 + 14) and low levels of PNP (respectively 1.9 + 0.8 and 2.5 _ 1.4). However no clear relationship appeared between subgroups of these T-cell malignancies defined by their patterns of surface antigens. revealed by reactivity with monoclonal antibodies, and ADA and PNP levels, and there was no correlation between the two enzymes. In contrast, cells from 31 patients with HLA-DR ÷ common ALL had significantly low values of ADA as compared to cells from six patients with HLA-DRcommon ALL and a linear correlation was observed between ADA and PNP in cells from children with non-T, non-B ALL. These results show that specific stages of T-cell development may be characterized by the relationships and the correlation between the two enzymes and suggest that TALL and T-LL appear to be the group of lymphoid malignancies with a high degree of incoordination between ADA and PNP activities.

Journal of Hepatology, 2003

Hepatology, 2004

Background. Nonrandom distribution of hepatitis C virus (HCV) quasispecies (compartmentalization ... more Background. Nonrandom distribution of hepatitis C virus (HCV) quasispecies (compartmentalization between blood plasma and leukocytes) suggests the presence of HCV leukotropic variants. HCV compartmentalization in the setting of liver transplantation (LT) is poorly understood. To study HCV leukotropic variants, we investigated the evolution of HCV compartmentalization after immunosuppression in liver transplant recipients. Methods. Plasma and peripheral blood mononuclear cell (PBMC) samples were collected from 5 liver transplant recipients before and after LT. We used clone sequencing to analyze the hypervariable region 1 (HVR1)-E2 384-419 region, which plays a key role in HCV entry and the induction of neutralizing responses, and assessed compartmentalization through phylogenetic analyses and Mantel's test. Results. Compartmentalization was frequent in the LT setting. HCV quasispecies were more homogeneous after LT in both the plasma and PBMC compartments, with a significant decrease in quasispecies complexity (P ϭ .003) and genetic distances (P ϭ .004) after transplantation. Our analysis identified 8 PBMC-related amino acid residues in HVR1. Conclusions. HCV compartmentalization between plasma and PBMCs and the emergence of leukotropic variants could be potentiated by immunosuppression in liver transplant recipients. The identification of defined leukotropic variants may contribute to the understanding of virus-host interactions after transplantation. End-stage cirrhosis related to chronic hepatitis C virus (HCV) infection has become the main indication for liver transplantation (LT). Virological recurrence is al

Blood, 2012

HIV infects activated CD4+ T cells and induces their depletion. Progressive HIV infection leading... more HIV infects activated CD4+ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNFα. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNFα production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3)+ and CD1c (BDCA-1)+ dendritic cell counts were reduced. Conversely, CD14+CD16++ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14++CD16−M-DC8− monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNFα in response to LPS than those from virologically suppre...

We show herein that B cell Ag receptor (BCR) triggering, but not stimulation by CD40 mAb and/or I... more We show herein that B cell Ag receptor (BCR) triggering, but not stimulation by CD40 mAb and/or IL-4, rapidly induced the coordinated expression of two closely related T cell chemoattractants, macrophage inflammatory protein-1 beta (MIP-1 beta) and MIP-1 alpha, by human B cells. Naive, memory, and germinal center B cells all produced MIP-1 alpha/beta in response to BCR triggering. In contrast to MIP-1 alpha/beta, IL-8, which is spontaneously produced by germinal center B cells but not by naive and memory B cells, was not regulated by BCR triggering. Culturing follicular dendritic cell-like HK cells with activated B cells did not regulate MIP-1 alpha/beta production, but it did induce production of IL-8 by HK cells. Microchemotaxis assays showed that CD4+CD45RO+ T cells of the effector/helper phenotype actively migrated along a chemotactic gradient formed by BCR-stimulated B cells. This effect was partially blocked by anti-MIP-1 beta and anti-CC chemokine receptor 5 Ab, but not by an...

Frontiers in Immunology

Memory B-cell dysfunctions and inefficient antibody response suggest germinal center (GC) impairm... more Memory B-cell dysfunctions and inefficient antibody response suggest germinal center (GC) impairments during HIV/SIV infection with possible contribution of overproduced B-cell activating factor (BAFF). To address this question, we compared proportions and functions of various B-cell subsets and follicular helper T-cells (T FH) in untreated (Placebo) and BR3-Fc treated (Treated) SIV-infected macaques. From day 2 post-infection (dpi), Treated macaques received one weekly injection of BR3-Fc molecule, a soluble BAFF antagonist, for 4 weeks. Whereas, the kinetics of CD4 + T-cell loss and plasma viral loads were comparable in both groups, BAFF blockade delayed the peak of inflammatory cytokines (CXCL10, IFNα), impaired the renewal of plasmacytoid dendritic cells and fostered the decline of plasma CXCL13 titers after 14 dpi. In Treated macaques, proportions of total and naïve B-cells were reduced in blood and spleen whereas SIV-induced loss of marginal zone (MZ) B-cells was only accentuated in blood and terminal ileum. Proportions of spleen GC B-cells and T FH were similar in both groups, with CD8 + T-cells and rare Foxp3 + being present in spleen GC. Regardless of treatment, sorted T FH produced similar levels of IL21, CXCL13, and IFNγ but no IL2, IL4, or BAFF and exhibited similar capacities to support IgG production by autologous or heterologous B-cells. Consistently, most T FH were negative for BAFF-R and TACI. Higher proportions of resting and atypical (CD21 lo) memory B-cells were present in Treated macaques compared to Placebo. In both groups, we found higher levels of BAFF-R expression on MZ and resting memory B-cells but low levels on atypical memory B-cells. TACI was present on 20-30% of MZ, resting and atypical memory B-cells in Placebo macaques. BAFF blockade decreased TACI expression on these B-cell subsets as well as titers of SIV-specific and vaccine-specific antibodies arguing for BAFF being mandatory for plasma cell survival. Irrespective of treatment, GC B-cells expressed BAFF-R at low level and were negative for TACI. In addition to key information on spleen BAFF-R and TACI expression, our data argue for BAFF contributing to the GC reaction in terminal ileum but being dispensable for the generation of atypical memory B-cells and GC reaction in spleen during T-dependent response against SIV.

Critical Reviews in Immunology

Interleukin 4 (IL4)-induced gene 1 (IL4I1) is an oxidase that degrades l-phenylalanine into pheny... more Interleukin 4 (IL4)-induced gene 1 (IL4I1) is an oxidase that degrades l-phenylalanine into phenylpyruvate, hydrogen peroxide, and ammonia. In contrast to other amino acid catabolic enzymes (i.e., indoleamine 2,3-dioxygenase and inducible nitric oxide synthase), IL4I1 is expressed not only in an intracellular form but also an active secreted form. Although about 20 yr ago IL4I1 was identified in murine B cells in response to IL4, we only recently established its key role in controlling B-cell receptor-mediated signaling during murine B-cell ontogeny and responses in physiological settings. Genetic IL4I1 invalidation increases the number of tumor-associated B cells and delays development of spontaneous metastatic melanoma in mice that are transgenic for the RET oncogene, without impairing tumor-specific antibody response. Although no consensus exists on phenotype and functions of melanoma-associated B cells, our results in RET mice argue for a protective role, with IL4I1 dampening this benefit. However, regulation of IL4I1 expression in innate-like and conventional B-cell subsets and its impact on B-cell properties are incompletely known, in particular, in cancer settings. This review aims to summarize our present knowledge of B cells in human and murine melanoma and address emerging questions about the impact of IL4I1 on B-cell functions in physiological and cancer settings. We note that during melanoma progression, IL4I1 may selectively be expressed by regulatory B cells and/or indirectly promote B-cell-mediated immunosuppression.

The Journal of investigative dermatology, Jan 23, 2018

Several studies have emphasized the importance of immune composition of the melanoma microenviron... more Several studies have emphasized the importance of immune composition of the melanoma microenvironment for the clinical outcome. The contribution of IL4-induced gene 1 (IL4I1), a phenylalanine oxidase with immunoregulatory functions, has not been yet explored. Here we studied a primary cutaneous melanoma series from stage I-III patients in order to investigate the association between in situ IL4I1 expression and clinical parameters or tumor infiltrating T-cell subsets. IL4I1 was detected in 87% of tumors and was mainly expressed by tumor-associated macrophages and very rare FoxP3 regulatory T cells (Tregs). The proportion of IL4I1 cells was higher in patients with an ulcerated melanoma or with a positive sentinel lymph node (sLN) and tended to correlate with a rapid relapse and shorter overall survival. This proportion also correlated positively with the presence of Tregs and negatively with the presence of cytotoxic CD8 T cells. The location of IL4I1 cells may also be relevant to pr...

Frontiers in immunology, 2017

With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing... more With the goal to design effective HIV vaccines, intensive studies focused on broadly neutralizing antibodies, which arise in a fraction of HIV-infected people. Apart from identifying new vulnerability sites in the viral envelope proteins, these studies have shown that a fraction of these antibodies are produced by self/poly-reactive B-cells. These findings prompted us to revisit the B-cell differentiation and selection process during HIV/SIV infection and to consider B-cells as active players possibly shaping the helper T-cell program within germinal centers (GCs). In this context, we paid a particular attention to B-cell-activating factor (BAFF), a key cytokine in B-cell development and immune response that is overproduced during HIV/SIV infection. As it does in autoimmune diseases, BAFF excess might contribute to the abnormal rescue of self-reactive B-cells at several checkpoints of the B-cell development and impair memory B-cell generation and functions. In this review, we first ...

Encyclopedia of Immunobiology, 2016

Antibody (Ab) responses are classified as T-dependent (TD) and T-independent responses according ... more Antibody (Ab) responses are classified as T-dependent (TD) and T-independent responses according to whether B cells receive T cell help. However, these two types of responses rely on different B cell subsets: follicular (FO) versus marginal zone (MZ) B cells, and occur in particular locations, B cell follicles versus spleen MZ. In contrast to FO B cells engaged in the TD response against protein antigens (Ags), MZ B cells preferentially recognize nonprotein Ags, rapidly produce poly/self-reactive IgM (or IgG) of low affinity for invading pathogens and eventually form nonproductive germinal centers but rarely generate long-lived plasma cells or memory B cells. Recent data show that MZ B cells receive key helper signals from neutrophils and type 3 innate-like cells within the MZ for mounting protective Ab responses. Being CD1 hi , MZ B cells can also present glycolipids to invariant natural killer T cell (iNKT) and establish cognate interactions leading to the production of glycolipid-specific Abs and iNKT activation. Through their continuous shuttling between MZ and follicles, MZ B cells can rapidly instruct FO B cells of any Ag change in MZ-associated blood flow. Here we highlight the phenotypic and functional particularities of MZ B cells in rodents and humans, and show how MZ B cells co-opt a diversity of innate helper cells, cleverly positioned in the MZ, to boost their Ab responses.

médecine/sciences, 1995

BCR : récepteur de la cellule B (B ce li receptor). TCR : récepteur de la cellule T (T cell recep... more BCR : récepteur de la cellule B (B ce li receptor). TCR : récepteur de la cellule T (T cell receptor). Ig : immunoglolrnline. ARH: motif d' homologie du récepteur de l' antigène. FeR : récepteur du fra gment Fe des Ig. PTK : protéine tyrosine kinase. PI3K: phosphatidylinositol-3-kinase. MAPK: mitogen activated protein kinase. Ras-GAP : Ras-GTPase activating protein. PL C: phospholipase C. I-P3 : inositol triphosphate. CD: classe de différenciation. CMH: complexe majeur d ' histocompatibilité. CSK : carboxyl stimulating kinase. Egr :f acteur de transcription précoce (early gene response). TNF : tumor necrosis factor. IL : interleukine. Th 1 et 2: ly mphocytes T auxiliaires (helper) .

The Journal of Immunology, 2014

full#ref-list-1 , 31 of which you can access for free at: cites 67 articles This article average ... more full#ref-list-1 , 31 of which you can access for free at: cites 67 articles This article average * 4 weeks from acceptance to publication Fast Publication! • Every submission reviewed by practicing scientists No Triage! • from submission to initial decision Rapid Reviews! 30 days* • Submit online.