The Stimulation of T Cells with Anti-CD2 Monoclonal Antibodies Facilitates the Induction of Polyclonal B-Cell Responses but does not Enhance the Activation of Antigen-Specific B Cells

1990 ◽  
Vol 31 (1) ◽  
pp. 25-31 ◽  
Author(s):  
R. TRIFILETTI ◽  
B. HYMAN ◽  
M. LaVIA ◽  
W. KNAPP ◽  
G. VIRELLA
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
B Cells ◽  
B Cell ◽  
Cell Responses ◽  
B Cell Responses ◽  
Stimulation Of

scholarly journals Ectopic Lymphoid Follicles in Multiple Sclerosis: Centers for Disease Control?

2020 ◽  
Vol 11 ◽  
Author(s):  
Austin Negron ◽  
Olaf Stüve ◽  
Thomas G. Forsthuber
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Memory B Cells ◽  
Lymphoid Follicles ◽  
Cell Responses ◽  
B Cell Responses

While the contribution of autoreactive CD4+ T cells to the pathogenesis of Multiple Sclerosis (MS) is widely accepted, the advent of B cell-depleting monoclonal antibody (mAb) therapies has shed new light on the complex cellular mechanisms underlying MS pathogenesis. Evidence supports the involvement of B cells in both antibody-dependent and -independent capacities. T cell-dependent B cell responses originate and take shape in germinal centers (GCs), specialized microenvironments that regulate B cell activation and subsequent differentiation into antibody-secreting cells (ASCs) or memory B cells, a process for which CD4+ T cells, namely follicular T helper (TFH) cells, are indispensable. ASCs carry out their effector function primarily via secreted Ig but also through the secretion of both pro- and anti-inflammatory cytokines. Memory B cells, in addition to being capable of rapidly differentiating into ASCs, can function as potent antigen-presenting cells (APCs) to cognate memory CD4+ T cells. Aberrant B cell responses are prevented, at least in part, by follicular regulatory T (TFR) cells, which are key suppressors of GC-derived autoreactive B cell responses through the expression of inhibitory receptors and cytokines, such as CTLA4 and IL-10, respectively. Therefore, GCs represent a critical site of peripheral B cell tolerance, and their dysregulation has been implicated in the pathogenesis of several autoimmune diseases. In MS patients, the presence of GC-like leptomeningeal ectopic lymphoid follicles (eLFs) has prompted their investigation as potential sources of pathogenic B and T cell responses. This hypothesis is supported by elevated levels of CXCL13 and circulating TFH cells in the cerebrospinal fluid (CSF) of MS patients, both of which are required to initiate and maintain GC reactions. Additionally, eLFs in post-mortem MS patient samples are notably devoid of TFR cells. The ability of GCs to generate and perpetuate, but also regulate autoreactive B and T cell responses driving MS pathology makes them an attractive target for therapeutic intervention. In this review, we will summarize the evidence from both humans and animal models supporting B cells as drivers of MS, the role of GC-like eLFs in the pathogenesis of MS, and mechanisms controlling GC-derived autoreactive B cell responses in MS.

scholarly journals The allogeneic bisection of carrier-specific enhancement of monoclonal B-cell responses.

1975 ◽  
Vol 142 (5) ◽  
pp. 1165-1179 ◽  
Author(s):  
S K Pierce ◽  
N R Klinman
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Immunoglobulin Class ◽  
Cell Responses ◽  
Cell Clones ◽  
Ia Antigens ◽  
Collaborative Interactions ◽  
B Cell Responses

The ability of T cells to enhance the response of syngeneic and allogeneic B cells to thymus-dependent hapten-carrier conjugates was analyzed. This analysis was carried out on individual primary B cells in splenic fragment cultures derived from irradiated reconstituted mice. This system has several advantages: (a) the response of the B cells is entirely dependent on carrier priming of the irradiated recipient; (b) this B-cell response can be quantitated in terms of the number of responding cells; and (c) very small B-cell responses can be readily detected and analyzed. The results indicate that the majority of hapten-specific B cells were stimulated in allogeneic and syngeneic recipients only if these recipients were previously carrier primed. The number of B cells responding in carrier-primed allogeneic recipients was 60-70% of that in syngeneic carrier-primed recipients. The antibody-forming cell clones resulting from B cells stimulated in the allogeneic environment produced small amounts of antibody and antibody solely of the IgM immunoglobulin class, while the larger responses in syngeneic recipients were predominantly IgG1 or IgM plus IgG1. The capacity of collaborative interactions between carrier-primed T cells and primary B cells to yield IgG1 antibody-producing clones was shown to be dependent on syngeny between these cells in the H-2 gene complex. It is concluded that: (a) B cells can be triggered by T-dependent antigens to clone formation through collaboration with T cells which differ at the H-2 complex as long as these T cells recognize the antigen; (b) the immunoglobulin class produced by the progeny of stimulated B cells generally depends on the nature of the stimulatory event rather than the nature of the B cell itself; and (c) stimulation to IgG1 production is dependent on syngeny between the collaborating T and B cells probably within the Ir-1A region. The role of the Ia antigens in the formation of IgG1-producing clones is not yet clear; Ia identity could permit IgG1 production or, conversely, nonidentity of Ia could induce all allogeneic interactions which prohibit IgG1 production.

scholarly journals An Early CD4+ T Cell–dependent Immunoglobulin A Response to Influenza Infection in the Absence of Key Cognate T–B Interactions

2003 ◽  
Vol 198 (7) ◽  
pp. 1011-1021 ◽  
Author(s):  
Mark Y. Sangster ◽  
Janice M. Riberdy ◽  
Maricela Gonzalez ◽  
David J. Topham ◽  
Nicole Baumgarth ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Cd4 T Cell ◽  
Mhc Ii ◽  
Cell Responses ◽  
Iga Response ◽  
B Cell Responses

Contact-mediated interactions between CD4+ T cells and B cells are considered crucial for T cell–dependent B cell responses. To investigate the ability of activated CD4+ T cells to drive in vivo B cell responses in the absence of key cognate T–B interactions, we constructed radiation bone marrow chimeras in which CD4+ T cells would be activated by wild-type (WT) dendritic cells, but would interact with B cells that lacked expression of either major histocompatibility complex class II (MHC II) or CD40. B cell responses were assessed after influenza virus infection of the respiratory tract, which elicits a vigorous, CD4+ T cell–dependent antibody response in WT mice. The influenza-specific antibody response was strongly reduced in MHC II knockout and CD40 knockout mice. MHC II–deficient and CD40-deficient B cells in the chimera environment also produced little virus-specific immunoglobulin (Ig)M and IgG, but generated a strong virus-specific IgA response with virus-neutralizing activity. The IgA response was entirely influenza specific, in contrast to the IgG2a response, which had a substantial nonvirus-specific component. Our study demonstrates a CD4+ T cell–dependent, antiviral IgA response that is generated in the absence of B cell signaling via MHC II or CD40, and is restricted exclusively to virus-specific B cells.

scholarly journals B cell resistance to Fas-mediated apoptosis contributes to their ineffective control by regulatory T cells in rheumatoid arthritis

2013 ◽  
Vol 74 (1) ◽  
pp. 294-302 ◽  
Author(s):  
Laetitia Rapetti ◽  
Konstantia-Maria Chavele ◽  
Catherine M Evans ◽  
Michael R Ehrenstein
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
B Cell ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Cell Resistance ◽  
Cell Responses ◽  
B Cell Responses

ObjectiveTo investigate whether regulatory T cells (Treg) can control B cell function in rheumatoid arthritis (RA) and if not to explore the basis for this defect.MethodsSuppression of B cell responses by Treg was analysed in vitro by flow cytometry and ELISA using peripheral blood mononuclear cells from 65 patients with RA and 41 sex-matched and aged-matched healthy volunteers. Blocking and agonistic antibodies were used to define the role of Fas-mediated apoptosis in B cell regulation.ResultsTreg failed to restrain B cell activation, proinflammatory cytokine and antibody production in the presence of responder T cells in RA patients. This lack of suppression was not only caused by impaired Treg function but was also due to B cell resistance to regulation. In healthy donors, control by Treg was associated with increased B cell death and relied upon Fas-mediated apoptosis. In contrast, RA B cells had reduced Fas expression compared with their healthy counterparts and were resistant to Fas-mediated apoptosis.ConclusionsThese studies demonstrate that Treg are unable to limit B cell responses in RA. This appears to be primarily due to B cell resistance to suppression, but Treg defects also contribute to this failure of regulation. Our data identify the Fas pathway as a novel target for Treg-mediated suppression of B cells and highlight a potential therapeutic approach to restore control of B cells by Treg in RA patients.

scholarly journals Antibody-specific immunoregulation

1977 ◽  
Vol 146 (2) ◽  
pp. 509-519 ◽  
Author(s):  
SK Pierce ◽  
NR Klinman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Regulatory Mechanism ◽  
Humoral Immune ◽  
Cell Responses ◽  
Donor Cells ◽  
Primary Donor ◽  
Fragment Culture ◽  
B Cell Responses ◽  
Stimulation Of

In recent years, much evidence has accumulated which demonstrates that an animal's immune system has the capacity to recognize its own antibody idiotypes. These findings suggest that self-idiotypic recognition may potentially play a role in the regulation of B-cell responses. The experiments presented in this report were carried out to determine if an animal develops the ability to specifically regulate the synthesis of antibodies specific for an antigen, subsequent to primary immunization to the particular antigen and concomitant with an initial antibody response. Employing the splenic fragment culture system we have compared the response of primary donor B cells in irradiated recipients which have been previously immunized to hemocyanin (Hy) alone or dinitrophenyl (DNP)-Hy plus Hy. The results indicated that only 25-30 percent of DNP- specific B cells stimulated by DNP-Hy in Hy immunized recipients could bestimulated by DNP-Hy in recipients immunized with Hy as well as DNP-Hy. B-cell responses to other haptens, such as fluoresceinated-Hy, and secondary DNP-specific B-cell responses were unaffected in DNP-Hy immunized animals. The nontrivial and specific nature of the observed decrease in primary DNP-specific B-cell responses was verified by the finding that the response of CB20 donor cells, which differ from BALB/c mice only in the immunoglobulin heavy chain allotype-linked locus, was unaffected in BALB/c recipient mice which had been immunized with DNP-Hy. Thus, it appeared that during a primary humoral immune response to a T- dependent antigen, an antibody-specific regulatory mechanism is induced which specifically limits the stimulation of hapten-specific primary, but not secondary, B cells. The important implications that these findings have for the understanding of the control of primary B-cell responses and the generation of secondary B cells is discussed.

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.

Food-allergic children have decreased peripheral regulatory B cells and altered B cell responses to IL-10

2021 ◽  
Vol 147 (2) ◽  
pp. AB3
Author(s):  
Adora Lin ◽  
Hemant Sharma ◽  
Pamela Guerrerio ◽  
Catherine Bollard
Keyword(s):  
B Cells ◽  
B Cell ◽  
Regulatory B Cells ◽  
Cell Responses ◽  
B Cell Responses

scholarly journals B cell depletion with anti-CD20 mAb exacerbates anti-donor CD4+ T cell responses in highly sensitized transplant recipients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asuka Tanaka ◽  
Kentaro Ide ◽  
Yuka Tanaka ◽  
Masahiro Ohira ◽  
Hiroyuki Tahara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
T Cell Responses ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Transplant Recipients ◽  
Cell Responses ◽  
Anti Cd20

AbstractPretransplant desensitization with rituximab has been applied to preformed donor-specific anti-human leukocyte antigen antibody (DSA)-positive recipients for elimination of preformed DSA. We investigated the impact of pretransplant desensitization with rituximab on anti-donor T cell responses in DSA-positive transplant recipients. To monitor the patients’ immune status, mixed lymphocyte reaction (MLR) assays were performed before and after desensitization with rituximab. Two weeks after rituximab administration, the stimulation index (SI) of anti-donor CD4+ T cells was significantly higher in the DSA-positive recipients than in the DSA-negative recipients. To investigate the mechanisms of anti-donor hyper responses of CD4+ T cells after B cell depletion, highly sensitized mice models were injected with anti-CD20 mAb to eliminate B cells. Consistent with clinical observations, the SI values of anti-donor CD4+ T cells were significantly increased after anti-CD20 mAb injection in the sensitized mice models. Adding B cells isolated from untreated sensitized mice to MLR significantly inhibited the enhancement of anti-donor CD4+ T cell response. The depletion of the CD5+ B cell subset, which exclusively included IL-10-positive cells, from the additive B cells abrogated such inhibitory effects. These findings demonstrate that IL-10+ CD5+ B cells suppress the excessive response of anti-donor CD4+ T cells responses in sensitized recipients.

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