scholarly journals A quantitative analysis of antigen-presenting cell function: activated B cells stimulate naive CD4 T cells but are inferior to dendritic cells in providing costimulation.

1994 ◽  
Vol 180 (5) ◽  
pp. 1829-1840 ◽  
Author(s):  
D J Cassell ◽  
R H Schwartz
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Quantitative Analysis ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Costimulatory Signals ◽  
Antigen Presenting ◽  
Activated B Cells

Ligation of CD28 on CD4 Th1 clones and freshly isolated mixtures of naive and memory CD4 T cells triggered their T cell receptors (TCR) is sufficient to induce the costimulatory signals necessary for interleukin 2 (IL-2) production by these cells. CTLA-4-reactive ligands expressed on antigen-presenting cells (APC) are critical in providing costimulatory signals to these T cell populations. We demonstrate that these activation characteristics apply equally to purified naive CD4 T cells. Because B cell blasts express CTLA-4-reactive ligands and high levels of adhesion and major histocompatibility complex class II molecules, they would be expected to engage both the TCR and CD28 and consequently stimulate IL-2 production by naive CD4 T cells. Using purified populations of cells in limiting dilution cultures, we have carried out a quantitative analysis of the interaction between naive CD4 T cells and either activated B or dendritic cells. We demonstrate that B cell blasts stimulate a high frequency of naive CD4 T cells. Slight differences in TCR signaling efficiency between the two APC types were observed. Even at optimal peptide concentrations, however, the amount of IL-2 made by individual T cells was fourfold lower in response to B cell blasts than to dendritic cells. This relative deficiency of activated B cells was due to their inability to optimally costimulate naive CD4 T cells.

scholarly journals T Cell Accumulation in B Cell Follicles Is Regulated by Dendritic Cells and Is Independent of B Cell Activation

2003 ◽  
Vol 197 (2) ◽  
pp. 195-206 ◽  
Author(s):  
Simon Fillatreau ◽  
David Gray
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
B Cell Activation ◽  
Cell Accumulation ◽  
Antigen Presenting ◽  
Deficient Mice

We investigated the mechanism of CD4 T cell accumulation in B cell follicles after immunization. Follicular T cell numbers were correlated with the number of B cells, indicating B cell control of the niche that T cells occupy. Despite this, we found no role for B cells in the follicular migration of T cells. Instead, T cells are induced to migrate into B cell follicles entirely as a result of interaction with dendritic cells (DCs). Migration relies on CD40-dependent maturation of DCs, as it did not occur in CD40-deficient mice but was reconstituted with CD40+ DCs. Restoration was not achieved by the activation of DCs with bacterial activators (e.g., lipopolysaccharide, CpG), but was by the injection of OX40L–huIgG1 fusion protein. Crucially, the up-regulation of OX40L (on antigen-presenting cells) and CXCR-5 (on T cells) are CD40-dependent events and we show that T cells do not migrate to follicles in immunized OX40-deficient mice.

Targeting STAT3 Signaling to Augment the Immunogenicity of B-Cell Lymphomas

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 708-708
Author(s):  
Hongwei Wang ◽  
F. Cheng ◽  
K. Wright ◽  
J. Tao ◽  
M. Smith ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Dna Binding ◽  
B Cell ◽  
Cd4 T Cells ◽  
Mutant Form ◽  
B Cell Lymphomas ◽  
Stat3 Signaling ◽  
Antigen Presenting

Abstract STAT3 signaling has emerged as a negative regulator of inflammatory responses in immune cells. In bone-marrow derived antigen-presenting cells (APCs), genetic or pharmacologic disruption of STAT3 led to inflammatory cells that effectively prime antigen-specific T-cell responses and restore the responsiveness of tolerized T-cells. In contrast, enhanced Stat3 activity in APCs resulted in increased production of the immunosuppressive cytokine IL-10 and induction of T-cell tolerance1. B-cell lymphomas being tumors derived from B-lymphocytes display intrinsic antigen-presenting capabilities. Augmentation of this APC function has been shown to result in effective anti-lymphoma immunity2. In this study we determined whether targeting Stat3 signaling might influence the intrinsic APC function of malignant B-cells and the responsiveness –or not- of antigen-specific CD4+ T-cells. First, we specifically block STAT3 signaling in A20 lymphoma B-cells by using a dominant negative variant of STAT3, Stat3b. Inhibition of STAT3 resulted in tumor cells capable not only of fully priming naïve antigen-specific CD4+T-cells but also able of restoring the responsiveness of tolerant T-cells from lymphoma bearing mice. Conversely, transfection of A20 B-cells with Stat3c, a constitutively activated mutant form of STAT3, led to T-cell unresponsiveness. Of note, manipulation of STAT3 in B cell tumors was associated with changes in the mRNA expression and protein levels of IL-10. Second, we evaluated the effects of two novel Stat3 inhibitors, CPA-7 (a platinum-containing compound that disrupts STAT3 DNA binding activity) and S3I-201 (inhibitor of Stat3:Stat3 complex formation and Stat3 DNA binding and transcriptional activities) in a murine model of Mantle Cell Lymphoma (MCL). In vitro treatment of FC-muMCL1 cells - derived from a tumor elicited in Em-Cyclin D1 transgenic mice- with increasing concentrations of either CPA-7 or S3I-201 resulted in an enhanced presentation of OVA-peptide to naïve CD4+ T-cells specific for a MHC class II restricted epitope of ovalbumin (OT-II cells). Indeed, these T-cells produce higher levels of IL-2 and IFN-gamma compared to anti-OVA T cells that encountered cognate antigen in untreated FC-muMCL1 cells. More importantly, MCL cells treated with CPA-7 restored the responsiveness of tolerized anti-OVA CD4+ T-cells. Finally, in vivo treatment of MCL-bearing mice with CPA-7 (5 mg/kg/iv given on days +21, +24 and +27 after tumor challenge) resulted in significant inhibition of p-Stat3 in malignant B-cells and augmentation of their APC function. Taken together, STAT3 signaling is involved in the regulation of the antigen-presenting capabilities of B-cell lymphomas and as such represents a novel molecular target to augment the immunogenicity of these tumors.

Primary Antigen-Specific B Cells: A Novel Approach to Cellular-Based Immunotherapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3717-3717
Author(s):  
Tahamtan Ahmadi ◽  
Nathalie Weizmann ◽  
Yvonne A. Efebera ◽  
David H. Sherr
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Mhc Class I ◽  
Class I ◽  
Protein Antigens ◽  
Cognate Protein ◽  
Activated B Cells

Abstract Background: The potential for CD40 ligand (CD40L)-activated B cells to serve as antigen-presenting cells (APC) for cell-based immunotherapy has been suggested. Unlike dendritic cells (DC), CD40L-activated B cell populations are readily expandable in vitro. In addition, antigen-specific B cells may efficiently uptake, process, and present cognate protein antigens. Nevertheless, important questions regarding the relative efficacy of CD40L-activated B cells as cell-based vaccines remain. Here, we exploited the unique ability of B cells to uptake antigen through their B cell receptor (BCR) and the propensity for CD40L-activated B cells, including antigen-specific clones, to grow in culture and to process cognate protein antigens to determine if CD40L-activated B cells represent a suitable substitute for dendritic cells for cell-based immunotherapy. Methods: As a head to head comparison between CD40L-activated B cells and mature DC, CD40L-activated B cells and bone marrow-derived DC were pulsed with MHC II- or MHC I-restricted self protein-derived (MOG; MBP) peptides and tested for their ability to induce proliferation of CD4+ or CD8+ clones. To compare processing and presentation of foreign protein antigens, C57BL/6 mice were immunized with 200 mg NP-BSA or an equivalent volume of PBS emulsified in CFA, sacrificed 10 days later and splenocytes obtained to generate antigen-specific CD40L-activated B cells and T cells. Bone marrow cells from PBS/CFA immunized mice were used to generate DCs. CD40L-activated (antigen-specific) B cells and DC were pulsed with NP-BSA, NP-CGG, or BSA and assayed for their ability to induce proliferation of primary T cells. Results: B cell populations were readily expanded by culture on CD40L transfected L cells. CD40L stimulation significantly up-regulated MHC class I and II expression and induced expression of CD80 and CD86 to levels similar to those detected on mature DCs. CD40L-activated B cells were comparable to DCs when presenting MHC class I- or II-restricted self-peptides to T cell clones. When presenting cognate protein antigen (NP-BSA or BSA) to primary T cells, CD40L-activated B cells from NP-BSA immunized mice were as efficient as DC, both of which induced a 13–15 fold increase in T cell proliferation. To determine if the hapten moiety is sufficient to increase antigen up-take and presentation, DCs and CD40L-activated B cells from NP-BSA immunized mice were pulsed with NP-CGG and used as APC for T cells from NP-BSA immunized mice. DCs induced significant responses comparable to those seen with BSA and NP-BSA. Activated B cells from NP-BSA-immunized mice induced significantly higher responses to NP-CGG than activated B cells from control PBS/CFA “immunized” mice, although these responses were lower than those generated with dendritic cells. Conclusion:CD40L-activated B cells can be readily expanded in vitroand significantly up-regulate co-stimulatory molecules CD80 and CD86 to levels comparable to mature DCs,CD40L-activated B cells present MHC class I- and II-restricted self-peptides to T cell clones as efficiently as mature DCs,Antigen-primed B cells are as efficient at presenting cognate protein antigens as DCs, Immunization with a hapten-carrier is sufficient to induce hapten-specific B cells which, when activated with CD40L, effectively present unrelated neoantigens conjugated with the hapten. The data suggest that CD40L-activated B cells represent an important alternative APC for immunotherapy, particularly when previously educated to protein or haptenic determinants.

Requirements for Co-Stimulation in T-Cell Dependent and T-Cell Independent Re-Stimulation of FVIII-Specific Memory B Cells

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 238-238 ◽  
Author(s):  
Aniko Ginta Pordes ◽  
Christina Hausl ◽  
Peter Allacher ◽  
Rafi Uddin Ahmad ◽  
Eva M Muchitsch ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Plasma Cells ◽  
Memory B Cells ◽  
Specific Memory ◽  
Stimulation Of

Abstract Memory B cells specific for factor VIII (FVIII) are critical for maintaining FVIII inhibitors in patients with hemophilia A. They are precursors of anti-FVIII antibody-producing plasma cells and are highly efficient antigen-presenting cells for the activation of T cells. The eradication of FVIII-specific memory B cells will be a prerequisite for any successful new approach to induce immune tolerance in patients with FVIII inhibitors. Little is known about the regulation of these cells. Previously we showed that ligands for toll-like receptors (TLR) 7 and 9 are able to re-stimulate FVIII-specific memory B cells in the absence of T-cell help. However, alternative “helper cells” such as dendritic cells are essential for providing help to memory B cells under such conditions. Based on these findings, we asked which co-stimulatory interactions are required for the restimulation of memory B cells in the presence of dendritic cells and ligands for TLR and whether these co-stimulatory interactions are the same as those required for the restimulation of memory B cells in the presence of activated T cells. We used spleen cells from hemophilic mice treated with human FVIII to generate highly purified populations of memory B cells, CD4+ T cells and dendritic cells. The required purity was achieved by a combination of magnetic bead separation and fluorescence-activated cell sorting. The memory B cell compartment was specified by the expression of CD19 together with IgG and the absence of surface IgM and IgD. Memory B cells were cultured in the presence of FVIII to stimulate their differentiation into anti-FVIII antibody-producing plasma cells. Different combinations of CD4+ T cells, ligands for TLR 7 and 9 and dendritic cells were added to the memory-B-cell cultures. Blocking antibodies and competitor proteins were used to specify the co-stimulatory interactions required for the re-stimulation of memory B cells in the presence of either CD4+ T cells or dendritic cells and ligands for TLR 7 and 9. Our results demonstrate that the blockade of B7-1 and B7-2 as well as the blockade of CD40L inhibit the re-stimulation of FVIII-specific memory B cells and their differentiation into anti-FVIII antibody-producing plasma cells in the presence of T-cell help. Similar requirements apply for the re-stimulation of memory B cells in the presence of dendritic cells and ligands for TLR 7 or 9. Dendritic cells in the absence of ligands for TLR are not able to provide help for the re-stimulation of memory B cells, which indicates that dendritic cells need to be activated. Furthermore, ligands for TLR 7 or 9 were not able to re-stimulate memory B cells in the complete absence of dendritic cells. Based on these results we conclude that dendritic cells activated by ligands for TLR 7 or 9 can substitute for activated CD4+ T cells in providing co-stimulatory help for memory-B-cell re-stimulation. CD40-CD40L interactions seem to be the most important co-stimulatory interactions for the re-stimulation of memory B cells, not only in the presence of activated CD4+ T cells but also in the presence of ligands for TLR and dendritic cells.

scholarly journals Response of naive antigen-specific CD4+ T cells in vitro: characteristics and antigen-presenting cell requirements.

1992 ◽  
Vol 176 (5) ◽  
pp. 1431-1437 ◽  
Author(s):  
M Croft ◽  
D D Duncan ◽  
S L Swain
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Cd4 Cells ◽  
Peptide Antigen ◽  
Naive T Cells ◽  
Naïve T Cells ◽  
Antigen Presenting

Because of the low frequency of T cells for any particular soluble protein antigen in unprimed animals, the requirements for naive T cell responses in specific antigens have not been clearly delineated and they have been difficult to study in vitro. We have taken advantage of mice transgenic for the V beta 3/V alpha 11 T cell receptor (TCR), which can recognize a peptide of cytochrome c presented by IEk. 85-90% of CD4+ T cells in these mice express the transgenic TCR, and we show that almost all such V beta 3/V alpha 11 receptor-positive cells have a phenotype characteristic of naive T cells, including expression of high levels of CD45RB, high levels of L-selectin (Mel-14), low levels of CD44 (Pgp-1), and secretion of interleukin 2 (IL-2) as the major cytokine. Naive T cells, separated on the basis of CD45RB high expression, gave vigorous responses (proliferation and IL-2 secretion) to peptide antigen presented in vitro by a mixed antigen-presenting cell population. At least 50% of the T cell population appeared to respond, as assessed by blast transformation, entry into G1, and expression of increased levels of CD44 by 24 h. Significant contributions to the response by contaminating memory CD4+ cells were ruled out by demonstrating that the majority of the CD45RB low, L-selectin low, CD44 high cells did not express the V beta 3/V alpha 11 TCR and responded poorly to antigen. We find that proliferation and IL-2 secretion of the naive CD4 cells is minimal when resting B cells present peptide antigen, and that both splenic and bone marrow-derived macrophages are weak stimulators. Naive T cells did respond well to high numbers of activated B cells. However, dendritic cells were the most potent stimulators of proliferation and IL-2 secretion at low cell numbers, and were far superior inducers of IL-2 at higher numbers. These studies establish that naive CD4 T cells can respond vigorously to soluble antigen and indicate that maximal stimulation can be achieved by presentation of antigen on dendritic cells. This model should prove very useful in further investigations of activation requirements and functional characteristics of naive helper T cells.

scholarly journals Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations

2016 ◽  
Vol 213 (11) ◽  
pp. 2413-2435 ◽  
Author(s):  
Yi Wang ◽  
Cindy S. Ma ◽  
Yun Ling ◽  
Aziz Bousfiha ◽  
Yildiz Camcioglu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Ex Vivo ◽  
Cell Phenotype ◽  
Loss Of Function ◽  
Inborn Errors

Combined immunodeficiency (CID) refers to inborn errors of human T cells that also affect B cells because of the T cell deficit or an additional B cell–intrinsic deficit. In this study, we report six patients from three unrelated families with biallelic loss-of-function mutations in RLTPR, the mouse orthologue of which is essential for CD28 signaling. The patients have cutaneous and pulmonary allergy, as well as a variety of bacterial and fungal infectious diseases, including invasive tuberculosis and mucocutaneous candidiasis. Proportions of circulating regulatory T cells and memory CD4+ T cells are reduced. Their CD4+ T cells do not respond to CD28 stimulation. Their CD4+ T cells exhibit a "Th2" cell bias ex vivo and when cultured in vitro, contrasting with the paucity of "Th1," "Th17," and T follicular helper cells. The patients also display few memory B cells and poor antibody responses. This B cell phenotype does not result solely from the T cell deficiency, as the patients’ B cells fail to activate NF-κB upon B cell receptor (BCR) stimulation. Human RLTPR deficiency is a CID affecting at least the CD28-responsive pathway in T cells and the BCR-responsive pathway in B cells.

Vaccine-elicited CD4 T cells prevent the deletion of antiviral B cells in chronic infection

2021 ◽  
Vol 118 (46) ◽  
pp. e2108157118
Author(s):  
Kerstin Narr ◽  
Yusuf I. Ertuna ◽  
Benedict Fallet ◽  
Karen Cornille ◽  
Mirela Dimitrova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Memory B Cells ◽  
Type I ◽  
Clonal Deletion ◽  
Cell Immunity ◽  
B Cell Immunity

Chronic viral infections subvert protective B cell immunity. An early type I interferon (IFN-I)–driven bias to short-lived plasmablast differentiation leads to clonal deletion, so-called “decimation,” of antiviral memory B cells. Therefore, prophylactic countermeasures against decimation remain an unmet need. We show that vaccination-induced CD4 T cells prevented the decimation of naïve and memory B cells in chronically lymphocytic choriomeningitis virus (LCMV)-infected mice. Although these B cell responses were largely T independent when IFN-I was blocked, preexisting T help assured their sustainability under conditions of IFN-I–driven inflammation by instructing a germinal center B cell transcriptional program. Prevention of decimation depended on T cell–intrinsic Bcl6 and Tfh progeny formation. Antigen presentation by B cells, interactions with antigen-specific T helper cells, and costimulation by CD40 and ICOS were also required. Importantly, B cell–mediated virus control averted Th1-driven immunopathology in LCMV-challenged animals with preexisting CD4 T cell immunity. Our findings show that vaccination-induced Tfh cells represent a cornerstone of effective B cell immunity to chronic virus challenge, pointing the way toward more effective B cell–based vaccination against persistent viral diseases.

scholarly journals IL-6 Production by Dendritic Cells Is Dispensable for CD8+Memory T-Cell Generation

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jean-François Daudelin ◽  
Mélissa Mathieu ◽  
Salix Boulet ◽  
Nathalie Labrecque
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
Memory T Cells ◽  
T Cell Memory ◽  
Memory Cells ◽  
Differential Outcome ◽  
Memory T Cell ◽  
Antigen Presenting

Following activation, naïve CD8+T cells will differentiate into effectors that differ in their ability to survive: some will persist as memory cells while the majority will die by apoptosis. Signals given by antigen-presenting cells (APCs) at the time of priming modulate this differential outcome. We have recently shown that, in opposition to dendritic cell (DC), CD40-activated B-(CD40-B) cell vaccination fails to efficiently produce CD8+memory T cells. Understanding why CD40-B-cell vaccination does not lead to the generation of functional long-lived memory cells is essential to define the signals that should be provided to naïve T cells by APCs. Here we show that CD40-B cells produce very low amount of IL-6 when compared to DCs. However, supplementation with IL-6 during CD40-B-cell vaccination did not improve memory generation. Furthermore, IL-6-deficient DCs maintained the capacity to promote the formation of functional CD8+effectors and memory cells. Our results suggest that in APC vaccination models, IL-6 provided by the APCs is dispensable for proper CD8+T-cell memory generation.

scholarly journals Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I.

1983 ◽  
Vol 158 (6) ◽  
pp. 2024-2039 ◽  
Author(s):  
M Howard ◽  
L Matis ◽  
T R Malek ◽  
E Shevach ◽  
W Kell ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
Cell Lines ◽  
Interleukin 2 ◽  
Activated T Lymphocytes ◽  
T Cell Lines ◽  
Activated B Cells

Antigen-activated T lymphocytes produce within 24 h of stimulation a factor that is indistinguishable biochemically and functionally from the B cell co-stimulating growth factor, BCGF-I, originally identified in induced EL4 supernatants: Supernatants from antigen-stimulated T cell lines are not directly mitogenic for resting B cells, but synergize in an H-2-unrestricted manner with anti-Ig activated B cells to produce polyclonal proliferation but not antibody-forming-cell development; biochemical studies reveal the B cell co-stimulating factor present in antigen-stimulated T cell line supernatants is identical by phenyl Sepharose chromatography and isoelectric focusing (IEF) to EL4 supernatant BCGF-I. We thus conclude that normal T cells produce BCGF-I in response to antigenic stimulation. Analysis of the mechanism of BCGF-I production by antigen-stimulated T cells showed that optimum amounts of BCGF-I were obtained as quickly as 24 h post-stimulation, and that the factor producing cells in the T cell line investigated bore the Lyt-1+2- phenotype. As few as 10(4) T cells produced sufficient BCGF-I to support the proliferation of 5 X 10(4) purified anti-Ig activated B cells. Finally, the activation of normal T cell lines to produce BCGF-I required either antigen presented in the context of syngeneic antigen-presenting cells (APC) or interleukin 2 (IL-2).

Donor B Cells in Transplants Augment Clonal Expansion and Persistence of Pathogenic Donor CD4+ T Cells in Autoimmune-Like Chronic Graft-Versus-Host Disease,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4021-4021
Author(s):  
James Sundblom Young ◽  
Tao Wu ◽  
Yuhong Chen ◽  
Dongchang Zhao ◽  
Heather F Johnston ◽  
...  
Keyword(s):  
T Cells ◽  
Salivary Gland ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Graft Versus Host Disease ◽  
Tissue Damage ◽  
Cd4 T Cells ◽  
Clonal Expansion ◽  
Graft Versus Host

Abstract Abstract 4021 Chronic graft-versus-host disease (cGVHD) manifests with autoimmune symptoms (i.e. increased serum levels of autoantibodies, donor T cell infiltration in skin and salivary gland tissues, and collagen deposition in skin tissues). Donor B cells have been indicated to play an important role in the pathogenesis of cGVHD in mouse models as well as in patients, but the mechanisms remain unclear. In the current studies, using a cGVHD mouse model of DBA/2 donor to MHC-matched BALB/c host, we have observed that donor B cells are activated by donor CD4+ T cells in transplants to upregulate MHC II and co-stimulatory molecules and produce IgG autoantibodies; in turn, donor B cells mediated clonal expansion of autoreactive donor-type CD4+ T cells, as judged by TCR spectratyping and in vitro T cell proliferation in response to donor- and host-type APCs. Kinetic studies showed that the presence of donor B cells in transplants was associated with persistence of GVHD target tissue damage (i.e. sclerodermatous skin) and persistence of donor CD4+ T infiltration in the tissues in which there is an expansion of Th1 and Th2 but not Th17. The presence of donor B cells in transplants also markedly augmented tissue damage in prototypical cGVHD targets such as the salivary gland. Sorted donor CD4+ T cells from primary recipients given donor B cell-containing transplants but not from the primary recipients given B cell-depleted transplants caused cGVHD-like tissue damage in the skin and salivary gland of adoptive recipients. These results indicate that donor B cells in bone marrow transplants play an important role in the generation and expansion of pathogenic CD4+ T cells that mediate chronic GVHD tissue damage. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document