NKT-cell help to B lymphocytes can occur independently of cognate interaction

Blood ◽  
2009 ◽  
Vol 113 (2) ◽  
pp. 370-376 ◽  
Author(s):  
Elena Tonti ◽  
Grazia Galli ◽  
Carmine Malzone ◽  
Sergio Abrignani ◽  
Giulia Casorati ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Interaction ◽  
Inkt Cells ◽  
Th Cells ◽  
Mhc Ii ◽  
Th Cell ◽  
Antibody Titers ◽  
Antigen Presenting

Abstract CD4+ T (Th)–cell help to B lymphocytes requires cognate interaction and CD40 engagement. Invariant natural killer T (iNKT) cells are innate-like T lymphocytes that recognize αgalactosylceramide (αGalCer) presented by CD1d, and can help B-cell responses. We asked whether αGalCer-activated iNKT cells help B lymphocytes through cognate interaction, or indirectly, via enhancement of Th-B–cell interaction. After immunization with protein Ags and αGalCer, antibody titers were assessed in wild-type or splenectomized mice, and in bone marrow radiation chimeras lacking CD1d or CD40 expression on B lymphocytes, or expressing CD1d or MHC II disjointly on antigen-presenting cells (APCs). We find that αGalCer-dependent enhancement of B-cell response (1) can occur when B cells do not express CD1d but express CD40; (2) requires that iNKT and Th cells interact with the same APCs that coexpress both CD1d and MHC-II; and (3) takes place without spleen. These findings demonstrate αGalCer-induced help for antibody responses can occur without cognate iNKT/B-cell interaction, and suggest this help entails activation of APCs by iNKT cells, which in turn activate Th cells and their helper functions for B cells. Thus, the αGalCer-induced help recapitulates the function of classical adjuvants that stimulate the innate immune system to support adaptive immune responses.

scholarly journals Role of the major histocompatibility complex in T cell activation of B cell subpopulations. A single monoclonal T helper cell population activates different B cell subpopulations by distinct pathways.

1982 ◽  
Vol 156 (2) ◽  
pp. 350-360 ◽  
Author(s):  
Y Asano ◽  
M Shigeta ◽  
C G Fathman ◽  
A Singer ◽  
R J Hodes
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Cell Interaction ◽  
T Helper Cell ◽  
T Helper ◽  
Th Cells ◽  
Histocompatibility Complex ◽  
Th Cell ◽  
Cell Subpopulations

It has recently been demonstrated that the Lyb-5+ and Lyb-5- B cell subpopulations differ in their requirements for major histocompatibility complex (MHC)-restricted activation by T helper (TH) cells. To determine whether these MHC-restricted and -unrestricted pathways of B cell activation result from differences in the participating TH cell populations or reflect differences exclusively in the responding B cell subpopulations, experiments were carried out using cloned TH cells for in vitro antibody responses to trinitrophenyl-keyhole limpet hemocyanin. The same cloned T helper cells were able to activate both CBA/N (Lyb-5-) B cells and CBA/CaHN (Lyb-5+ + Lyb-5-) B cells under different experimental conditions. The activation of Lyb-5-B cells by cloned T helper cells required both MHC-restricted TH cell-B cell interaction and carrier-hapten linkage. In contrast, the activation of Lyb-5+ B cells required only MHC-restricted T helper cell interaction with accessory cells, while T-B interaction was MHC unrestricted and did not require carrier-hapten linkage. Thus, the differences in activation requirements observed for the Lyb-5- and Lyb-5+ B cell subsets do not result from differences in the TH cell populations activating these B cells, but rather reflect differences in the ability of these B cells to respond to signals from the same TH cells.

scholarly journals Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

1990 ◽  
Vol 171 (6) ◽  
pp. 2153-2158 ◽  
Author(s):  
J R Tumang ◽  
D N Posnett ◽  
B C Cole ◽  
M K Crow ◽  
S M Friedman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Cell Activation ◽  
Cell Interaction ◽  
Class Ii ◽  
B Cell Differentiation ◽  
Th Cells ◽  
Human B Cells ◽  
Th Cell

Experimentally induced murine graft-vs.-host disease may be characterized by hypergammaglobulinemia, autoantibody formation, and immune complex-mediated organ system damage that mimics SLE. These autoimmune phenomena are mediated by abnormal Th-B cell cooperation, across MHC disparities, in which donor-derived allospecific Th cells recognize and interact with MHC class II antigens on the surface of recipient B cells. Microbial toxins, termed superantigens, which bind to MHC class II molecules and activate selected T cells based on TCR variable gene usage, may induce a similar form of Th-B cell interaction. In the present study, we generated and characterized human Th cell lines reactive with the Mycoplasma arthritidis superantigen (MAM). The essential observation is that resting human B cells bind MAM and present it to superantigen-reactive autologous or allogeneic Th cells, resulting in both Th cell activation and a consequent polyclonal Ig response by the superantigen-bearing B cells.

scholarly journals CELL INTERACTIONS IN THE IMMUNE RESPONSE IN VITRO

1972 ◽  
Vol 136 (4) ◽  
pp. 737-760 ◽  
Author(s):  
Marc Feldmann
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Interaction ◽  
T And B Lymphocytes ◽  
Activated T Cells ◽  
Cell Cooperation

The mechanism of interaction of T and B lymphocytes was investigated in an in vitro hapten carrier system using culture chambers with two compartments separated by a cell impermeable nucleopore membrane. Because specific cell interaction occurred efficiently across this membrane, contact of T and B lymphocytes was not essential for cooperation which must have been mediated by a subcellular component or "factor." By using different lymphoid cell populations in the lower culture chamber and activated thymus cells in the upper chamber (with antigen present in both), it was found that the antigen-specific mediator acted indirectly on B cells, through the agency of macrophages. Macrophages which had been cultured in the presence of activated T cells and antigen acquired the capacity to specifically induce antibody responses in B cell-containing lymphoid populations. Trypsinization of these macrophages inhibited their capacity to induce immune responses, indicating that the mediator of cell cooperation is membrane bound. By using antisera to both the haptenic and carrier determinants of the antigen as blocking reagents, it was demonstrated that the whole antigen molecule was present on the surface of macrophages which had been exposed to activated T cells and antigen. Because specifically activated T cells were essential a component of the antigen-specific mediator must be derived from these cells. By using anti-immunoglobulin sera as inhibitors of the binding of the mediator to macrophages, the T cell component was indeed found to contain both κ- and µ-chains and was thus presumably a T cell-derived immunoglobulin. It was proposed that cell cooperation is mediated by complexes of T cell IgM and antigen, bound to the surface of macrophage-like cells, forming a lattice of appropriately spaced antigenic determinants. B cells become immunized by interacting with this surface. With this mechanism of cell cooperation, the actual pattern of antigen-B cell receptor interactions in immunization would be the same with both thymus-dependent and independent antigens. An essential feature of the proposed mechanism of cell cooperation is that macrophage-B cell interaction must occur at an early stage of the antibody response, a concept which is supported by many lines of evidence. Furthermore this mechanism of cell interaction can be elaborated to explain certain phenomena such as the highly immunogenic macrophage-bound antigen, antigenic competition, the distinction between immunity and tolerance in B lymphocytes, and the possible mediation of tolerance by T lymphocytes.

scholarly journals Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.

1983 ◽  
Vol 158 (2) ◽  
pp. 265-279 ◽  
Author(s):  
K Bottomly ◽  
B Jones ◽  
J Kaye ◽  
F Jones
Keyword(s):  
T Cells ◽  
B Cells ◽  
Cell Surface ◽  
B Cell ◽  
Cell Activation ◽  
Cell Surface Expression ◽  
Th Cells ◽  
Th Cell ◽  
Ia Antigens

We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.

scholarly journals Polyclonal stimulation of resting B lymphocytes by antigen-specific T lymphocytes.

1984 ◽  
Vol 159 (3) ◽  
pp. 861-880 ◽  
Author(s):  
A L DeFranco ◽  
J D Ashwell ◽  
R H Schwartz ◽  
W E Paul
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Lymphocytes ◽  
Cell Interaction ◽  
T Cell Stimulation ◽  
Cross Linkage ◽  
Immune Defect ◽  
Antigen Presenting

Resting B lymphocytes are activated, proliferate, and differentiate into antibody-secreting cells when cultured with long-term lines of major histocompatibility complex (MHC)-restricted, antigen-specific T cell in the presence of the antigen for which the T cells are specific. Under optimal conditions, essentially all B cells are activated and approximately 35% enter S phase in the absence of antigens for which the B cells are specific. Activation and proliferation are observed in cells from both normal mice and mice with the xid-determined immune defect. Highly purified B cells bearing Ia molecules for which the T cells are "cospecific" can present antigen to T cells with the resulting T cell stimulation leading to the activation and proliferation of the antigen-presenting B cells. However, B cells that do not bear Ia molecules for which the T cells are cospecific are also activated and proliferate if antigen and a source of antigen-presenting B cells or macrophage-rich cells of proper histocompatibility type are present. Thus, resting B cells, both normal and "xid", can be activated by non-MHC restricted factors without receptor cross-linkage. Experiments are presented that support the concept that local production and action of such unrestricted activating factors may be responsible for the MHC-restriction of T cell-B cell interaction seen in many circumstances.

scholarly journals Therapeutic Targeting of Autoreactive B Cells: Why, How, and When?

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 83
Author(s):  
Zachary C. Stensland ◽  
John C. Cambier ◽  
Mia J. Smith
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Immune Suppression ◽  
Immune Defense ◽  
B Cell Depletion ◽  
Therapeutic Targeting ◽  
Autoreactive B Cells ◽  
Antigen Presenting ◽  
Self Antigen

B lymphocytes play critical roles in the development of autoimmunity, acting as autoantibody manufacturers, antigen-presenting cells, and producers of cytokines. Pan-B cell depletion has demonstrated efficacy in treatment of many autoimmune disorders, but carries with it an unfavorable safety profile due to global immune suppression. Hence, attention has turned to the potential of autoantigen-specific B cell targeted therapies, which would deplete or silence pathogenic self-antigen-reactive cells while sparing B cells needed for immune defense. Here, we discuss the antigen-specific B cell-targeted approaches that are under development or are under consideration, that could be employed to allow for more precise therapy in the treatment of autoimmunity. Lastly, we discuss some of the challenges associated with antigen-specific B cell targeting that may impact their clinical applicability.

scholarly journals CD19+ B Lymphocytes Are Predictive for Anti-Sars-Cov-2 Vaccination Response in Multiple Myeloma Patients

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3788-3788
Author(s):  
Susanne Ghandili ◽  
Martin Schönlein ◽  
Heiko Becher ◽  
Christian Wiessner ◽  
Marc Lütgehetmann ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Research Funding ◽  
B Lymphocyte ◽  
Medicine Research ◽  
Cell Numbers ◽  
Vaccination Response ◽  
Antibody Titers

Abstract Introduction: Up to now,reliable results regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with multiple myeloma (MM), especially under current myeloma-directed therapy, are scarcely available. Here, we report an analysis describing the level of post-vaccination antibody titers after the 1 stand 2 ndanti-SARS-CoV-2 vaccination depending on therapy, remission status, and B- and T-cell numbers in patients with MM and related plasma cell neoplasia. Methods: This observational single-center study included patients aged ≥18 years with diagnoses of MM, monoclonal gammopathies of clinical significance (MGCS), or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations. Patients with prior COVID-19 infections were excluded. Samples were analyzed for the presence of SARS-CoV-2 specific antibodies using the quantitative anti-spike IgG (SARS-CoV-2 spike RBD IgG, cut off ≥ 0.8 BAU/ml) according to manufacturer's recommendations. SARS-CoV-2 spike protein antibody titer (SP-AbT) were evaluated after at least 7 days after the 1 stand 2 ndvaccination, respectively. This study was performed between January 1 - July 15, 2021, at the University Medical Center Hamburg-Eppendorf, Germany, as part of the COVIDOUT trial (NCT04779346). All patients provided written informed consent. Aims of this study were to evaluate a possible correlation between SP-AbT and CD19+ B lymphocyte count, as well as to identify other factors impacting vaccination response. Results: 82 patients who received SARS-CoV-2 vaccines (including 67 patients with mRNA-, 8 with vector-based vaccines and 4 heterologous vaccinations) were included. 74 patients had diagnosis of MM, 4 of MGCS/smoldering MM and 4 of AL. Median age was 68 years (range 35-85) and 49 patients were male. In total, 37 patients (45.1%) received anti-CD38- and 2 (2.4%) anti-SLAMF7-targeting therapies at the time of vaccination, 52 (63.4%) patients received immunomodulatory drug (IMID)-based treatments and 13 patients (15.9%) were under active surveillance. 59% of patients had newly diagnosed and 41% refractory or relapsed disease. In total, 75.6% of all patients were in deep remissions (very good partial remission or better). Assessment of anti-SARS-CoV-2 antibody titers took place in median 23 days (range [r] 8-63 days) after the 1 stand 21 days (r: 6-53) after the 2 ndvaccination. A positive SARS-CoV-2 SP-AbT was detected in 31.9% of assessable patients with an overall median SP-AbT of 0 BAU/ml (r: 0-10328, mean 202.36) after the 1 stvaccination and increased up to 88.9% (median SP-AbT of 216.87 BAU/ml, r: 0-25720, mean 2139.29) after 2 ndvaccination. Of the patients not showing positive SP-AbT after the 1 stvaccination, 80.9% became positive after 2 ndvaccination, while 19.1 % remained negative. Median SP-AbT titer was significantly lower compared to patients who became positive already after 1 stvaccination (51.04 vs. 2191.87 BAU/ml, p<0.0001). Regarding immune status, a CD19+ B cell count of median 33.5/µl (r: 1-696/µl) was seen in the overall patient cohort; in patients with negative SP-AbT, median CD19+ B cell numbers were significantly lower compared to patients with positive titers (median CD19+ B cells: 2.0 vs. 52.5/µl, p=0.005). Overall, CD19+ B lymphocyte numbers correlate significantly with positive SP-AbT results and were identified as predictive factor in multivariate analysis. The previously suggested threshold of 30 CD19+ B cells/µl as being predictive for SP-AbT development could be validated. SP-AbT concentration was significantly lower with older age. Furthermore, median SP-AbT were significantly lower in patients with current anti-CD38 directed therapy (median SP-AbT: 1085.4 vs. 62.05 BAU/ml, p < 0.005). Conclusions: In spite of immunodeficiency and immunosuppressive therapy, most MM patients develop SP-AbT. However, about 11% of MM patients failed to develop SP-AbT after full vaccination, and thus remain on risk for COVID-19. Higher counts of CD19+ B lymphocytes, with a threshold of 30 CD19+ B lymphocytes/µl, are predictive for SP-AbT formation and may further help to identify patients at higher risk of insufficient vaccination response in whom control of vaccination success and potential third vaccination are particularly important. Disclosures Bokemeyer: GlaxoSmithKline: Research Funding; Inside: Research Funding; IO Biotech: Research Funding; Eisai: Research Funding; Daiichi Sankyo: Research Funding; Gilead Sciences: Research Funding; Blueprint Medicine: Research Funding; BerGenBio: Research Funding; Janssen-Cilag: Research Funding; Isofol Medical: Research Funding; AOK Health insurance: Consultancy; GSO: Consultancy; Bayer Schering Pharma: Consultancy; Gylcotope GmbH: Research Funding; ADC Therapeutics: Research Funding; Apellis Pharmaceuticals: Research Funding; Amgen: Research Funding; Alexion Pharmaceuticals: Research Funding; Agile Therapeutics: Research Funding; Merck Serono: Consultancy, Other: Travel accomodation ; Lilly/ImClone: Consultancy; Merck Sharp Dohme: Consultancy, Honoraria; AstraZeneca: Honoraria, Research Funding; BMS: Honoraria, Other: Travel accomodation, Research Funding; Bayer: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel accomodation; Merck KGaA: Honoraria; Abbvie: Research Funding; Boehringer Ingelheim: Research Funding; Celgene: Research Funding; Astellas: Research Funding; Karyopharm Therapeutics: Research Funding; Lilly: Research Funding; Millenium: Research Funding; MSD: Research Funding; Nektar: Research Funding; Rafael Pharmaceuticals: Research Funding; Springworks Therapeutics: Research Funding; Taiho Pharmaceutical: Research Funding; Pfizer: Other. Sinn: Incyte: Honoraria, Research Funding; Pfizer: Honoraria; Servier: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Astra Zenica: Consultancy, Research Funding; MSD: Consultancy, Research Funding; Sanofi: Consultancy; Bayer: Research Funding; BMS: Honoraria, Research Funding. Leypoldt: GSK: Consultancy, Other: Meeting attendance ; Sanofi: Consultancy; Abbvie: Other: Meeting attendance . Weisel: Adaptiv Biotec: Consultancy; Abbvie: Consultancy; BMS: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Honoraria; Novartis: Honoraria; Oncopeptides: Consultancy, Honoraria; Pfizer: Honoraria; Roche: Honoraria; Takeda: Honoraria; Sanofi: Consultancy, Honoraria, Research Funding.

LITAF, a BCL6 Target Gene, Regulates Autophagia in B Cells and Is Essential for T-Cell Dependent Humoral Responses

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1391-1391 ◽  
Author(s):  
Cristina Bertolo ◽  
Raquel Malumbres ◽  
Ainara Sagardoy ◽  
Eloy F Robles ◽  
Jose I Martinez-Ferrandis ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoma Cells ◽  
Mhc Ii

Abstract Abstract 1391 LITAF was discovered as a p53-induced transcript that promoted TNFa secretion in monocytes in response to LPS. We previously reported that LITAF is inactivated by deletion or promoter hypermethylation in germinal center-derived B-cell lymphomas. However, the function of LITAF in B lymphocytes is unknown. Using gene expression analysis of isolated B-cell subpopulation and immunohistochemical studies of tonsil lymphoid follicles we found that LITAF is expressed in naïve B lymphocytes and is repressed within the germinal centers (GCs). Thus, LITAF showed an opposite expression to BCL6, an essential regulator of GC development and function. Likewise, expression of LITAF and BCL6 were inversely correlated in cell lines and biopsies from patients with B-cell lymphoma, further suggesting a link between LITAF and BCL6. ChIP-on-chip and ChIP-sequencing analyses of B cells coupled with luciferase reporter assays revealed that BCL6 repressed LITAF expression by binding to its promoter. Accordingly, BCL6 silencing with siRNAs or after exposure to a BCL6-inhibitor peptide increased LITAF expression, indicating that LITAF is transcriptionally repressed by BCL6 in GC B lymphocytes and in B-cell lymphoma cells. To initially elucidate the function of LITAF in B cells, gain-and-loss of function experiments were performed in different cellular models. LITAF expression was not related to TNFa secretion after LPS exposure, nor modulated cell proliferation or apoptosis in B cells. However, sustained expression of LITAF in B-cell lymphoma cells increased cell size, lysosome content and mitochondrial mass. Gene expression microarray studies defined a LITAF-related transcriptional signature containing genes involved in the regulation of endomembranes, vesicle trafficking and protein transport. Accordingly, immunofluorescence analysis co-localized LITAF with lysosomes and with autophagosomes expressing LC3, the mammalian homolog of yeast autophagy-related protein (Atg8), as well as with the lysosomal sorting-associated proteins NEDD4 and TSG101, both in normal CD19+ B lymphocytes and in B-cell lymphoma cells. In addition, LITAF expression induced autophagic activity in B cells, shown by an increase in the FL1/FL3 ratio after acridine orange staining and by converting LC3-I to LC3-II, which were more evident upon cell starvation. Together, these data suggest that LITAF may play a role in the processing of proteins in autophagosomes through regulating autophagy. To investigate LITAF function in vivo, we generated mice with targeted deletion of the Litaf gene in B lymphocytes by using the Cre-loxP system. Litaf -mb1-Cre (Litaf−/− ) mice developed healthy and showed normal distribution of hematopoietic cell subpopulations. However, Litaf−/− mice were unable to develop full T-cell dependent immune responses, presenting PNA-stained, Litaf-negative GCs that were absent or had marked reduction in size and number. Accordingly, reduced amounts of IgM, IgG1 and IgG3 antibodies as a consequence of abnormal class switch recombination (CSR) were detected in immunized mice. However, in experiments testing CSR in vitro, in which B cells are artificially activated in the absence of T cells, the amounts of IgM/IgG1/IgG3 did not differ between knock-out and control groups. Similarly, mouse immunization with a T-cell independent antigen did not induce differences in immunoglobulin production. Further studies of GCs in T-cell immunized Litaf−/− mice using an antibody for the Class II-associated invariant chain peptide (CLIP) revealed that the atrophic GCs in Litaf−/− mice showed strong CLIP expression in comparison to wild-type littermates. In normal immune responses, CLIP peptides bind to MHC class II molecules in endolysosomes, until they are displaced by the antigen, then releasing CLIP and allowing MHC II-antigen complexes to be transported to the cell membrane for T-cell presentation. The failure to develop appropriate immune responses together with the accumulation of CLIP peptides in Litaf -deficient mice indicate that Litaf is essential for adequate T-cell dependent immune responses in GC B lymphocytes, possibly through facilitating the presentation of the antigens to MHC II molecules in the endolysosomes. Once this process is assembled and the T-cell activated B lymphocytes enter the GCs, BCL6 represses LITAF to prevent additional interactions between B and T cells during BCR editing. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Small splenic B cells that bind to antigen-specific T helper (Th) cells and face the site of cytokine production in the Th cells selectively proliferate: immunofluorescence microscopic studies of Th-B antigen-presenting cell interactions.

1994 ◽  
Vol 179 (5) ◽  
pp. 1507-1515 ◽  
Author(s):  
H Kupfer ◽  
C R Monks ◽  
A Kupfer
Keyword(s):  
B Cells ◽  
B Cell ◽  
Specific Antigen ◽  
Cell Interactions ◽  
T Helper ◽  
Microtubule Organizing Center ◽  
Th Cells ◽  
Activating Receptors ◽  
Microscopic Studies ◽  
Antigen Presenting

Antigen (Ag)-specific T helper (Th) cells regulate the proliferation and differentiation of Ag-specific B cells by secreting cytokines and by expressing activating receptors like gp39. In vitro, the cytokines and the activating receptors function in an Ag-nonspecific manner. It is unclear, therefore, how Ag specificity is imposed on B cell responses in physiological Th-B cell interactions. Here we studied, at the single cell level, the interactions between cloned Th cells and small splenic B cells, which served as Ag-specific antigen-presenting cells (APCs) to the Th cells. Digital confocal immunofluorescence microscopy of Th-B cell conjugates revealed significant variability in the molecular and cellular properties of these interactions, in spite of the fact that all the interactions in this system were expected to be Ag specific. After 30 h of incubation B cells began to divide, and this process was entirely dependent on the presence of both Th cells and Ag. Immunofluorescence microscopic studies showed that essentially all the mitotic B cells were bound to Th cells and faced the microtubule organizing center (MTOC) in the Th cells where interleukin 4 was highly concentrated. Other B cells that were bound to the same Th cells but were not close to the Th-MTOC remained in interphase. These results provide the first direct structural and functional evidence that the site of interaction of B cells with Th cells affects their immune response. We propose that, during Ag-induced Th-B cell interactions, B cells that are bound facing the Th-MTOC proliferate preferentially because they are the recipients of locally secreted cytokines. In addition, these B cells may interact with newly expressed receptors, which may also be locally inserted into the Th membrane. The polarized delivery of activating molecules towards the Th-bound APCs may impose functional specificity on effector molecules that otherwise are not Ag specific.

scholarly journals The role of B cells in regulation of Th cell differentiation in Coxsackievirus B3-Induced Acute Myocarditis

2021 ◽  
Author(s):  
Zhihong Cen ◽  
Yong Li ◽  
Bin Wei ◽  
Weifeng Wu ◽  
Yanlan Huang ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Th17 Cells ◽  
Th2 Cells ◽  
Cardiac Damage ◽  
Th Cells ◽  
Th22 Cells ◽  
Th Cell

Abstract Background:Viral myocarditis (VMC) is the major cause of sudden death in adolescents. To date, no effective treatment has been identified for VMC. Studies have shown that T helper (Th) cells such as Th1, Th2, Th17, and Th22 cells are involved in the pathogenesis of VMC. However, the role of B cells and their impact on Th cells in VMC is unclear. In this study, we investigated the role of B cells in Th cell differentiation in myocardial damage in an animal model of VMC.Methods and Results:C57BL/6 mice were infected with Coxsackievirus B3 (CVB3) intraperitoneally or injected with phosphate-buffered saline as a control condition. At day 7, samples from these mice were analyzed by histology, ELISA, flow cytometry, and gene expression assays. We found that TNF-α-, IL-6-, and IL-17-producing B cell numbers were significantly increased, while IL-4-producing B cell population was significantly reduced in acute VMC. Furthermore, we performed B cell knockout (BKO), SCID, and SCID+B cells reconstitution experiments. We found that BKO alleviated the cardiac damage following CVB3 infection, may hamper the differentiation of Th1 and Th17 cells, may promote the differentiation of Th2 cells, and proved ineffective for the differentiation of Th22 cells. In contrast, SCID+B cells reconstitution experiment exacerbated the cardiac damage. Ex vivo studies further revealed that B cells promote the differentiation of Th1 and Th17 cells and inhibit the differentiation of Th2 cells.Conclusions:Our study shows that B cells are activated and have strong abilities of antigen presentation and producing cytokines in VMC; B cells not only play a pathogenic role in VMC independent of T cells, but also promote Th1 and Th17 cell differentiation, and hamper Th2 cell differentiation in VMC.

Sign in / Sign up

Export Citation Format

Share Document