scholarly journals FUNCTIONAL CHARACTERISTICS OF PEYER'S PATCH LYMPHOID CELLS

1974 ◽  
Vol 139 (2) ◽  
pp. 407-413 ◽  
Author(s):  
Martin F. Kagnoff ◽  
Paul Billings ◽  
Melvin Cohn
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Adherent Cells ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Cell Induction ◽  
Membrane Bound

This study shows that LPS is not mitogenic in cultures containing B cells, or B cells and accessory adherent cells or ME, unless T cells are present. This observation rules out models of induction of antibody synthesis in which it is assumed that the delivery of a mitogenic signal by the interaction of LPS with the membrane of the B cell is in itself sufficient for B-cell induction (19). Further, it makes unlikely the proposed extrapolation of such a model to other so-called thymus-independent antigens, e.g., PVP, levan, dextran, and SIII (19). The mitogenic action of LPS appears to be due to its ability to complete an inductive stimulus to B cells (13). We interpret the observed thymus dependence of the B-cell response to LPS in light of a model in which two signals are obligatory for B-cell induction (14). The first signal in the inductive pathway is delivered to the antigen-sensitive cell via a conformational change in the receptor upon interaction with antigen. The second signal is delivered via the thymus-derived cooperating system. Since LPS can induce immune responses to both immunogenic and nonimmunogenic ligands (9–13) we envision that one signal is delivered to the B cell via specific binding of the ligand to the B-cell antigen receptor, while a second signal is delivered as a result of T-cell cooperation via membrane-bound LPS. This has been termed abnormal induction (20). In this example LPS is the foreign membrane-bound determinant in question although histocompatibility antigens (21, 22), viral determinants, or surface bound lectins could act similarly. In light of the above model, one observation should be pointed out. LPS inhibits the induction of a SRBC response in normal Peyer's patch cells to which adherent cells or ME is added. This inhibition appears to be a T-cell-mediated effect because it is abolished by partial depletion of the T-cell population by antitheta treatment. Since the induction of IgM producing PFC is being measured, the T-cell-dependent LPS inhibition could act either (a) by induction of T-cell "suppression" (23, 24) of the normal cooperating system required for a SRBC response, or (b) by the induction of such high levels of cooperating function (13) as to be inhibitory to a SRBC IgM response. Our observations contrast sharply with prior reports which describe LPS as a thymus-independent antigen (2–4) and a B-cell mitogen (5–8) capable of stimulating immune responses in the absence of T-cell cooperation (2–12). This demonstration of the thymus dependence of LPS stimulation has been possible because Peyer's patches from congenitally athymic (nude) mice are functionally a highly purified B-cell population devoid of T cells and accessory adherent cells. In this respect, earlier studies relied on nude spleen cultures and spleen cultures from thymectomized, lethally irradiated, and bone marrow-reconstituted mice (3, 4, 6–13). These spleen cultures which contain B cells and accessory adherent cells are recognized to be deficient but not devoid of the thymus-derived contribution to the inductive stimulus (12, 13). It could be argued that the presence of T cells and adherent cells is in fact required for the antigen-specific effect and not for the LPS effect. However, this is unlikely since our experiments show that LPS is not directly mitogenic for B cells and does not stimulate background anti-SRBC PFC. It seems unlikely that Peyer's patch antigen-sensitive cells differ from antigen-sensitive cells in the spleen in their mechanism of induction. We have shown that Peyer's patch B cells can be specifically induced by antigen, and Peyer's patch T cells mediate cooperating and killer functions. Alternately, the possibility that Peyer's patch B cells were not stimulated by LPS as a result of prior cryptic exposure to LPS (13) in the intestinal tract was excluded since cultures containing B cells, T cells, and adherent cells or ME were stimulated to DNA synthesis by LPS. The reason that certain antigens appear to be thymus independent may be that their repeating polymeric nature permits inductive interactions at very low levels of thymus-derived cooperation (see reference 20 for quantitative considerations). It has been stated that the inductive properties of all thymus-independent antigens are directly related to their ability to act as B-cell mitogens (19). The observation that LPS is thymus dependent for its B-cell mitogenic activity makes us question the thymus independence of any antigen.

scholarly journals The Role of Chemokines in the Microenvironmental Control of T versus B Cell Arrest in Peyer's Patch High Endothelial Venules

2000 ◽  
Vol 191 (1) ◽  
pp. 77-88 ◽  
Author(s):  
R.A. Warnock ◽  
J.J. Campbell ◽  
M.E. Dorf ◽  
A. Matsuzawa ◽  
L.M. McEvoy ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Target Domain ◽  
High Endothelial Venules ◽  
Circulating Lymphocytes ◽  
Cell Arrest

Chemokines have been hypothesized to contribute to the selectivity of lymphocyte trafficking not only as chemoattractants, but also by triggering integrin-dependent sticking (arrest) of circulating lymphocytes at venular sites of extravasation. We show that T cells roll on most Peyer's patch high endothelial venules (PP-HEVs), but preferentially arrest in segments displaying high levels of luminal secondary lymphoid tissue chemokine (SLC) (6Ckine, Exodus-2, thymus-derived chemotactic agent 4 [TCA-4]). This arrest is selectively inhibited by functional deletion (desensitization) of CC chemokine receptor 7 (CCR7), the receptor for SLC and for macrophage inflammatory protein (MIP)-3β (EBV-induced molecule 1 ligand chemokine [ELC]), and does not occur in mutant DDD/1 mice that are deficient in these CCR7 ligands. In contrast, pertussis toxin–sensitive B cell sticking does not require SLC or MIP-3β signaling, and occurs efficiently in SLClow/− HEV segments in wild-type mice, and in the SLC-negative HEVs of DDD/1 mice. Remarkably, sites of T and B cell firm adhesion are segregated in PPs, with HEVs supporting B cell accumulation concentrated in or near follicles, the target domain of most B cells entering PPs, whereas T cells preferentially accumulate in interfollicular HEVs. Our findings reveal a fundamental difference in signaling requirements for PP-HEV recognition by T and B cells, and describe an unexpected level of specialization of HEVs that may allow differential, segmental control of lymphocyte subset recruitment into functionally distinct lymphoid microenvironments in vivo.

Chronic Lymphocytic Leukemia Cells Acquire a Regulatory B-Cell Phenotype Modified By PD1 Signaling

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3319-3319 ◽  
Author(s):  
Shimrit Ringelstein-Harlev ◽  
Irit Avivi ◽  
Shoham Shivtiel-Arad ◽  
Tami Katz
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
Immune Modulation ◽  
Lymphocytic Leukemia ◽  
T Cell Proliferation ◽  
Cell Contact

Abstract Introduction: Chronic lymphocytic leukemia (CLL) cells utilize several mechanisms of survival, some propagating proliferation and preventing apoptosis through intrinsic cell cycle signals, and others suppressing anti-tumor immune responses. Patients often present with a predominant population of regulatory T-cells (Tregs), and general features of T-cell exhaustion. Given the unique phenotype of CLL cells and the observed T-cell abnormalities we hypothesized that these cells function as regulatory B-cells (Bregs). Bregs, mostly explored in the autoimmune disease setting, produce interleukin-10 (IL10), which mediates attenuation of effector T-cell responses and enhances regulatory activity. These features have also been suggested to be responsible for weakening of anti-tumor immune responses. Breg activation requires stimulation of various combinations of Toll-like receptors (TLRs), the B-cell receptor (BCR) and CD40. Our previous studies have demonstrated that TLR9-stimulated CLL cells "acquire" Breg markers as well as PD1 and PDL1, which, while not being classic Breg discriminators, are established players in immune modulation. Moreover, such stimulation resulted in inhibition of proliferation of autologous T-cells. The current study aimed to further explore the regulatory characteristics of CLL cells focusing on additional suppressive mechanisms that may have a role in CLL immune evasion, particularly, the PD1/PDL1 axis. Methods: B-cells were isolated from peripheral blood mononuclear cells (PBMCs) of untreated CLL patients (Rai stages 0-IV). These B-CLL cells were stimulated with TLR-9 agonist (ODN) or CD40 ligand (CD40L) followed by their co-culture with isolated autologous CD4+ T cells. The regulatory features of B-CLL cells were studied by testing their effect on T cells. Their proliferation was evaluated using the CFSE method following stimulation with anti-CD3/CD28 antibodies and IL2; induction of Tregs (CD4+CD25highFoxp3+ population) was assessed by FACS analysis. The involvement of the PD1/PDL1 axis was examined by incubating B-cells with antiPD1 neutralizing antibodies prior to co-culture. Cell contact dependence was evaluated by plating B-cells in hanging cell culture inserts denying B and T cell contact while allowing flow of small soluble molecules. Results: CLL cells stimulated with ODN or CD40L, induced a significant increase in Tregs: 1.35±0.1-fold (p=0.03, N=12) for ODN and 1.7±0.2-fold (p=0.008, N=14) for CD40L, occurring in 68% and 80% of patients, respectively, while co-culture with unstimulated B-CLL cells did not result in the expansion of the Treg population. Treg induction was observed only under contact conditions (N=5), suggesting that this regulatory function requires cell-to-cell contact and cannot be carried out solely by secreted factors like IL10. Neutralization of PD1 on CLL B-cells affects both Treg induction and T-cell proliferation. Following CD40L stimulation, a 1.3-fold reduction in Treg percentage was observed when PD1 signaling was blunted (N=10). In contrast, PD1 blockage of ODN-stimulated CLL cells did not reduce Treg induction; however, it did adversely affect inhibition of T-cell proliferation (10%-decrease in inhibited T-cells; N=6). Conclusions: CLL cells "acquire" a Breg phenotype and function, inhibiting T-cell proliferation and inducing Tregs. These properties, while working together to promote immune regulation and cancer evasion, are elicited by different ligands in the cell environment and are likely to be mediated via separate pathways. The involvement of B-cell-associated PD1 in the induction of Tregs and inhibition of T-cell proliferation suggests a biologic role of PD1 signaling in CLL cells, strengthening the Breg phenotype. The current study has shown that CLL cells recruit several mechanisms operating cooperatively to support immune modulation and promote their survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals Preferential induction of polyclonal IgA secretion by murine Peyer's patch dendritic cell-T cell mixtures.

1984 ◽  
Vol 160 (3) ◽  
pp. 941-946 ◽  
Author(s):  
D M Spalding ◽  
S I Williamson ◽  
W J Koopman ◽  
J R McGhee
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
B Cells ◽  
Dendritic Cell ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Cellular Mechanisms

Polyclonal IgA secretion is inducible in murine B cells when DC-T from Peyer's patches (PP) provide the inducing stimulus. PP DC-T, which are composed predominantly of dendritic cells and Lyt-1+ T cells, are capable of dramatic augmentation of IgA secretion by PP or spleen B cells with minimal induction of IgM secretion. DC-T from spleen, however, are incapable of augmenting IgA secretion by either PP or spleen B cells. The level of IgA secretion is dependent upon the dose of DC-T providing the inducing stimulus and reaches a plateau with DC-T:B ratios of less than 1:1. This system for preferential induction of IgA responses should permit elucidation of cellular mechanisms involved in regulation of IgA secretion.

scholarly journals Functional characteristics of Peyer's patch cells. III. Carrier priming of T cells by antigen feeding.

1975 ◽  
Vol 142 (6) ◽  
pp. 1425-1435 ◽  
Author(s):  
M F Kagnoff
Keyword(s):  
T Cells ◽  
B Cell ◽  
Peyer's Patches ◽  
Peyer’S Patches ◽  
Peyer’S Patch ◽  
Peyer's Patch ◽  
Antibody Synthesis ◽  
Humoral Antibody ◽  
Cell Induction

Peyer's patch T cells may serve an important role in the interaction of the host with intraluminal gut antigens. Studies presented in this paper demonstrate that T cells in murine Peyer's patches can be carrier primed for helper function in the induction of an antihapten response by feeding antigen. Carrier priming was assessed by measuring the ability of Peyer's patch cells from mice fed heterologous erythrocytes to enhance an antitrinitrophenyl (TNP) response in vitro when added to normal Peyer's patch cells cultured with TNP coupled to the erythrocyte used for feeding. Priming of T helper cells in Peyer's patches was antigen specific and occurred when erythrocytes were administered orally but not when erythrocytes were injected intravenously or intraperitoneally. Murine Peyer's patches are naturally deficient in a cooperating accessory adherent cell type(s) required for B-cell induction to humoral antibody synthesis in vitro and antigen feeding does not result in significant induction of Peyer's patch B cells to humoral antibody synthesis in vivo. Since Peyer's patch T cells can be carrier-antigen primed for helper function in the absence of B-cell induction to humoral antibody synthesis, these studies may indicate that T-cell priming is less dependent than B-cell induction on cooperating accessory adherent cells.

scholarly journals B cell depletion impairs vaccination-induced CD8+ T cell responses in a type I interferon-dependent manner

2021 ◽  
pp. annrheumdis-2021-220435
Author(s):  
Theresa Graalmann ◽  
Katharina Borst ◽  
Himanshu Manchanda ◽  
Lea Vaas ◽  
Matthias Bruhn ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Expansion ◽  
De Novo ◽  
T Cell Responses ◽  
Type I ◽  
Cell Responses ◽  
T Cell Expansion

ObjectivesThe monoclonal anti-CD20 antibody rituximab is frequently applied in the treatment of lymphoma as well as autoimmune diseases and confers efficient depletion of recirculating B cells. Correspondingly, B cell-depleted patients barely mount de novo antibody responses during infections or vaccinations. Therefore, efficient immune responses of B cell-depleted patients largely depend on protective T cell responses.MethodsCD8+ T cell expansion was studied in rituximab-treated rheumatoid arthritis (RA) patients and B cell-deficient mice on vaccination/infection with different vaccines/pathogens.ResultsRituximab-treated RA patients vaccinated with Influvac showed reduced expansion of influenza-specific CD8+ T cells when compared with healthy controls. Moreover, B cell-deficient JHT mice infected with mouse-adapted Influenza or modified vaccinia virus Ankara showed less vigorous expansion of virus-specific CD8+ T cells than wild type mice. Of note, JHT mice do not have an intrinsic impairment of CD8+ T cell expansion, since infection with vaccinia virus induced similar T cell expansion in JHT and wild type mice. Direct type I interferon receptor signalling of B cells was necessary to induce several chemokines in B cells and to support T cell help by enhancing the expression of MHC-I.ConclusionsDepending on the stimulus, B cells can modulate CD8+ T cell responses. Thus, B cell depletion causes a deficiency of de novo antibody responses and affects the efficacy of cellular response including cytotoxic T cells. The choice of the appropriate vaccine to vaccinate B cell-depleted patients has to be re-evaluated in order to efficiently induce protective CD8+ T cell responses.

scholarly journals The role of H-2-linked genes in helper T cell function. VII. Expression of I region and immune response genes by B cells in bystander help assays.

1980 ◽  
Vol 152 (5) ◽  
pp. 1274-1288 ◽  
Author(s):  
P Marrack ◽  
J W Kappler
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Function ◽  
High Responder ◽  
Helper T Cells ◽  
Spleen Cells ◽  
Region Gene ◽  
Immunoglobulin Receptor

The mode of action by bystander helper T cells was investigated by priming (responder X nonresponder) (B6A)F1 T cells with poly-L-(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(TG)-A--L] and titrating the ability of these cells to stimulate an anti-sheep red blood cell (SRBC) response of parental B cells and macrophages in the presence of (TG)-A--L. Under limiting T cell conditions, and in the presence of (TG)-A--L, (TG)-A--L-responsive T cells were able to drive anti-SRBC responses of high-responder C57BL/10.SgSn (B10) B cells and macrophages (M0), but not of low-responder (B10.A) B cells and M0. Surprisingly, the (TG)-A--L-driven anti-SRBC response of B10.A B cells was not restored by addition of high-responder acessory cells, in the form of (B6A)F1 peritoneal or irradiated T cell-depleted spleen cells, or in the form of B10 nonirradiated T cell-depleted spleen cells. These results suggested that (TG)-A--L-specific Ir genes expressed by B cells controlled the ability of these cells to be induced to respond to SRBC by (TG)-A--L-responding T cells, implying that direct contact between the SRBC-binding B cell precursor and the (TG)-A--L-responsive helper T cells was required. Analogous results were obtained for keyhold limpet hemocyanin (KLH)-driven bystander help using KLH-primed F1 T cells restricted to interact with cells on only one of the parental haplotypes by maturing them in parental bone marrow chimeras. It was hypothesized that bystander help was mediated by nonspecific uptake of antigen [(TG)-A--L or KLH] by SRBC-specific b cells and subsequent display of the antigen on the B cell surface in association with Ir of I-region gene products, in a fashion similar to the M0, where it was then recognized by helper T cells. Such an explanation was supported by the observation that high concentrations of antigen were required to elicit bystander help. This hypothesis raises the possibility of B cell processing of antigen bound to its immunoglobulin receptor and subsequent presentation of antigen to helper T cells.

scholarly journals Early Reconstitution of Antibody Secreting Cells after Allogeneic Stem Cell Transplantation

2022 ◽  
Vol 11 (1) ◽  
pp. 270
Author(s):  
Martina Hinterleitner ◽  
Clemens Hinterleitner ◽  
Elke Malenke ◽  
Birgit Federmann ◽  
Ursula Holzer ◽  
...  
Keyword(s):  
Innate Immunity ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Antibody Secreting Cells

Immune cell reconstitution after stem cell transplantation is allocated over several stages. Whereas cells mediating innate immunity recover rapidly, adaptive immune cells, including T and B cells, recover slowly over several months. In this study we investigated kinetics and reconstitution of de novo B cell formation in patients receiving CD3 and CD19 depleted haploidentical stem cell transplantation with additional in vivo T cell depletion with monoclonal anti-CD3 antibody. This model enables a detailed in vivo evaluation of hierarchy and attribution of defined lymphocyte populations without skewing by mTOR- or NFAT-inhibitors. As expected CD3+ T cells and their subsets had delayed reconstitution (<100 cells/μL at day +90). Well defined CD19+ B lymphocytes of naïve and memory phenotype were detected at day +60. Remarkably, we observed a very early reconstitution of antibody-secreting cells (ASC) at day +14. These ASC carried the HLA-haplotype of the donor and secreted the isotypes IgM and IgA more prevalent than IgG. They correlated with a population of CD19− CD27− CD38low/+ CD138− cells. Of note, reconstitution of this ASC occurred without detectable circulating T cells and before increase of BAFF or other B cell stimulating factors. In summary, we describe a rapid reconstitution of peripheral blood ASC after CD3 and CD19 depleted haploidentical stem cell transplantation, far preceding detection of naïve and memory type B cells. Incidence before T cell reconstitution and spontaneous secretion of immunoglobulins allocate these early ASC to innate immunity, eventually maintaining natural antibody levels.

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