scholarly journals Gut T cell–independent IgA responses to commensal bacteria require engagement of the TACI receptor on B cells

2020 ◽  
Vol 5 (49) ◽  
pp. eaat7117 ◽  
Author(s):  
E. K. Grasset ◽  
A. Chorny ◽  
S. Casas-Recasens ◽  
C. Gutzeit ◽  
G. Bongers ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Gut Microbiota ◽  
B Cell ◽  
Immunoglobulin A ◽  
Cd40 Ligand ◽  
Commensal Bacteria ◽  
Secretory Immunoglobulin A ◽  
Follicular Helper ◽  
Secretory Immunoglobulin

The gut mounts secretory immunoglobulin A (SIgA) responses to commensal bacteria through nonredundant T cell–dependent (TD) and T cell–independent (TI) pathways that promote the establishment of mutualistic host-microbiota interactions. SIgAs from the TD pathway target penetrant bacteria, and their induction requires engagement of CD40 on B cells by CD40 ligand on T follicular helper cells. In contrast, SIgAs from the TI pathway bind a larger spectrum of bacteria, but the mechanism underpinning their production remains elusive. Here, we show that the intestinal TI pathway required CD40-independent B cell–activating signals from TACI, a receptor for the innate CD40 ligand–like factors BAFF and APRIL. TACI-induced SIgA responses targeted a fraction of the gut microbiota without shaping its overall composition. Of note, TACI was dispensable for TD induction of IgA in gut-associated lymphoid organs. Thus, BAFF/APRIL signals acting on TACI orchestrate commensal bacteria–specific SIgA responses through an intestinal TI program.

Commensal bacteria coated by secretory immunoglobulin A and immunoglobulin G in the gastrointestinal tract of pigs and calves

2012 ◽  
Vol 83 (12) ◽  
pp. 799-804 ◽  
Author(s):  
Takeshi TSURUTA ◽  
Ryo INOUE ◽  
Takamitsu TSUKAHARA ◽  
Mitsunori NAKAMOTO ◽  
Hiroshi HARA ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Immunoglobulin G ◽  
Immunoglobulin A ◽  
Commensal Bacteria ◽  
Secretory Immunoglobulin A ◽  
Secretory Immunoglobulin

T cell-intrinsic Interferon Regulatory Factor-1 expression suppresses differentiation of CD4 + T cell populations that support chronic gammaherpesvirus infection.

2021 ◽  
Author(s):  
C. N. Jondle ◽  
K. E. Johnson ◽  
W. P. Mboko ◽  
V. L. Tarakanova
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Germinal Center ◽  
T Cell Subsets ◽  
Viral Reservoir ◽  
B Cell Differentiation ◽  
Follicular Helper ◽  
Interferon Regulatory Factor 1 ◽  
Latent Viral Reservoir

Gammaherpesviruses are ubiquitous pathogens that establish life-long infection and are associated with B cell lymphomas. To establish chronic infection, these viruses usurp B cell differentiation and drive a robust germinal center response to expand the latent viral reservoir and gain access to memory B cells. Germinal center B cells, while important for the establishment of latent infection, are also thought to be the target of viral transformation. The host and viral factors that impact the gammaherpesvirus-driven germinal center response are not clearly defined. We showed that global expression of the antiviral and tumor-suppressor interferon regulatory factor 1 (IRF-1) selectively attenuates the murine gammaherpesvirus 68 (MHV68)-driven germinal center response and restricts expansion of the latent viral reservoir. In this study we found that T cell intrinsic IRF-1 expression recapitulates some aspects of antiviral state imposed by IRF-1 during chronic MHV68 infection, including attenuation of the germinal center response and viral latency in the spleen. We also discovered that global and T cell-intrinsic IRF-1 deficiency leads to unhindered rise of IL-17A-expressing and follicular helper T cell populations, two CD4 + T cell subsets that support chronic MHV68 infection. Thus, this study unveils a novel aspect of antiviral activity of IRF-1 by demonstrating IRF-1-mediated suppression of specific CD4 + T cell subsets that support chronic gammaherpesvirus infection. Importance Gammaherpesviruses infect over 95% of the adult population, last the lifetime of the host, and are associated with multiple cancers. These viruses usurp the germinal center response to establish lifelong infection in memory B cells. This manipulation of B cell differentiation by the virus is thought to contribute to lymphomagenesis, though exactly how the virus precipitates malignant transformation in vivo is unclear. IRF-1, a host transcription factor and a known tumor suppressor, restricts the MHV68-driven germinal center response in a B cell-extrinsic manner. We found that T cell intrinsic IRF-1 expression attenuates the MHV68-driven germinal center response by restricting the CD4 + T follicular helper population. Further, our study identified IRF-1 as a novel negative regulator of IL-17-driven immune responses, highlighting the multifaceted role of IRF-1 in gammaherpesvirus infection.

scholarly journals Antigen-presenting ILC3 regulate T cell–dependent IgA responses to colonic mucosal bacteria

2019 ◽  
Vol 216 (4) ◽  
pp. 728-742 ◽  
Author(s):  
Felipe Melo-Gonzalez ◽  
Hana Kammoun ◽  
Elza Evren ◽  
Emma E. Dutton ◽  
Markella Papadopoulou ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antigen Presentation ◽  
Immunoglobulin A ◽  
Lymphoid Cells ◽  
Host Interactions ◽  
Commensal Microbiota ◽  
Follicular Helper ◽  
Cell Class ◽  
Antigen Presenting

Intestinal immune homeostasis is dependent upon tightly regulated and dynamic host interactions with the commensal microbiota. Immunoglobulin A (IgA) produced by mucosal B cells dictates the composition of commensal bacteria residing within the intestine. While emerging evidence suggests the majority of IgA is produced innately and may be polyreactive, mucosal-dwelling species can also elicit IgA via T cell–dependent mechanisms. However, the mechanisms that modulate the magnitude and quality of T cell–dependent IgA responses remain incompletely understood. Here we demonstrate that group 3 innate lymphoid cells (ILC3) regulate steady state interactions between T follicular helper cells (TfH) and B cells to limit mucosal IgA responses. ILC3 used conserved migratory cues to establish residence within the interfollicular regions of the intestinal draining lymph nodes, where they act to limit TfH responses and B cell class switching through antigen presentation. The absence of ILC3-intrinsic antigen presentation resulted in increased and selective IgA coating of bacteria residing within the colonic mucosa. Together these findings implicate lymph node resident, antigen-presenting ILC3 as a critical regulatory checkpoint in the generation of T cell–dependent colonic IgA and suggest ILC3 act to maintain tissue homeostasis and mutualism with the mucosal-dwelling commensal microbiota.

scholarly journals High-fat diet reduces the level of secretory immunoglobulin A coating of commensal gut microbiota

2019 ◽  
Vol 38 (2) ◽  
pp. 55-64 ◽  
Author(s):  
Teresia Aluoch MUHOMAH ◽  
Naoki NISHINO ◽  
Emiko KATSUMATA ◽  
Wu HAOMING ◽  
Takeshi TSURUTA
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Immunoglobulin A ◽  
Secretory Immunoglobulin A ◽  
High Fat ◽  
Secretory Immunoglobulin

Cultured Human B Cell APCs Expanded Using Il-4 and CD40 Ligand Preferentially Promote a Type 2 T Cell Response to Alloimmune Stimulation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2668-2668
Author(s):  
Abdul Tawab ◽  
Yoshiyuki Takahashi ◽  
Childs Richard ◽  
Kurlander J. Roger
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Response ◽  
Cd40 Ligand ◽  
T Cell Response ◽  
Ifn Γ

Abstract In vitro stimulation of human peripheral blood B cells with recombinant IL-4 and CD40 ligand (CD40L) markedly increases their expression of MHC and costimulatory molecules, thus enhancing antigenic peptide presentation to T cells. Because these cells proliferate extensively in vitro (unlike monocytes or dendritic cells), they represent a promising and convenient reagent for the generation and maintenance of antigen-specific T cells for use in a variety of experimental or therapeutic settings. However, the impact of this type of B cell APC on cytokine production by responder T cells has hitherto not been examined. To address this issue, we stimulated normal human T cells with either allogeneic B cells (generated in vitro) or with MNCs obtained from the same donor. After 7 days, T cells were washed and re-challenged with the same APCs. The resulting alloreactive cytokine response was measured using quantitative ELISPOT methods and expressed as the frequencies of IFN-γ, IL-4, and IL-5 producing cells per thousand responder cells added. B cell- and MNC-primed cell lines both produced vigorous lymphokine responses, but B cell-stimulated T cells consistently produced more IL-5 spots (mean of 265 vs. 98/1000 responders, p<0.002) and fewer IFN-γ spots (163 vs 386/1000 cells, p<0.005) than MNC-stimulated cells. Further, the ratio of IFN-γ to IL-5 spots was almost ten-fold lower in B cell-stimulated cultures compared to MNC-induced cultures (0.67 vs. 5.2, p<0.001). ELISPOT studies assessing the ratio of IFN-γ to IL-4 spots and ELISA assays comparing IFN-γ and IL-5 levels from culture supernatants demonstrated the same pattern of marked type 2 skewing by B cells. This pattern was unaffected by the presence of anti-IL-4 antibody suggesting type 2 skewing was not mediated by IL-4. Cytokine skewing produced by B cells or MNC could be partially reversed by swapping MNC and B cells during re-stimulation on day 7, but this plasticity was markedly reduced after 3 (weekly) cycles of B cell or MNC re-stimulation in vitro. Type 2 skewing by B cells was enhanced when monocytes were removed from responder T cell populations by either depleting CD14+ positive cells or by positive selection of T cells prior to stimulation. In contrast, type 2 polarization could be prevented using recombinant IL-12. Not all cells of B-cell origin share the same propensity to type 2 skewing observed with IL-4/CD40L-stimulated B cells; under identical conditions, EBV-transformed B cells stimulated alloimmune T cells to produce a strong type 1 cytokine response comparable to that produced by MNCs. In summary, IL-4/CD40L-stimulated B cells strongly promote a type 2 T cell response during primary alloimmune challenge; this skewing can become fixed after repeated B cell stimulation. Investigators using these cells as APC should be aware of this potential phenomenon, particularly during primary T cell responses. It is also important to consider the factors described above that may exacerbate or ameliorate this effect.

scholarly journals Clearance of Citrobacter rodentium Requires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

2004 ◽  
Vol 72 (6) ◽  
pp. 3315-3324 ◽  
Author(s):  
Christian Maaser ◽  
Michael P. Housley ◽  
Mitsutoshi Iimura ◽  
Jennifer R. Smith ◽  
Bruce A. Vallance ◽  
...  
Keyword(s):  
B Cells ◽  
Host Defense ◽  
Immunoglobulin A ◽  
Mucosal Inflammation ◽  
Secretory Immunoglobulin A ◽  
J Chain ◽  
Crypt Hyperplasia ◽  
Deficient Mice ◽  
Secretory Antibodies ◽  
Secretory Immunoglobulin

ABSTRACT Citrobacter rodentium, a murine model pathogen for human enteropathogenic Escherichia coli, predominantly colonizes the lumen and mucosal surface of the colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice infected with C. rodentium develop a secretory immunoglobulin A (IgA) response, but the role of B cells or secretory antibodies in host defense is unknown. To address this question, we conducted oral C. rodentium infections in mice lacking B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice showed peak bacterial numbers in colon and feces at 1 week and bacterial eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible initially but could not control infection subsequently. Tissue responses showed marked differences, as infection of normal mice was accompanied by transient crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6 weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6 weeks. The functions of B cells were not mediated by secretory antibodies, since mice lacking IgA or secreted IgM or proteins required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally. Nonetheless, systemic administration of immune sera reduced bacterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this effect. These results indicate that host defense against C. rodentium depends on B cells and IgG antibodies but does not require production or transepithelial transport of IgA or secreted IgM.

scholarly journals Rapid Emergence of T Follicular Helper and Germinal Center B Cells Following Antiretroviral Therapy in Advanced HIV Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun-Shu Wong ◽  
Clarisa M. Buckner ◽  
Silvia Lucena Lage ◽  
Luxin Pei ◽  
Felipe L. Assis ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Antiretroviral Therapy ◽  
B Cell ◽  
Germinal Center ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
Cd4 T Cell ◽  
Follicular Helper ◽  
Cell Counts

Low nadir CD4 T-cell counts in HIV+ patients are associated with high morbidity and mortality and lasting immune dysfunction, even after antiretroviral therapy (ART). The early events of immune recovery of T cells and B cells in severely lymphopenic HIV+ patients have not been fully characterized. In a cohort of lymphopenic (CD4 T-cell count &lt; 100/µL) HIV+ patients, we studied mononuclear cells isolated from peripheral blood (PB) and lymph nodes (LN) pre-ART (n = 40) and 6-8 weeks post-ART (n = 30) with evaluation of cellular immunophenotypes; histology on LN sections; functionality of circulating T follicular helper (cTfh) cells; transcriptional and B-cell receptor profile on unfractionated LN and PB samples; and plasma biomarker measurements. A group of 19 healthy controls (HC, n = 19) was used as a comparator. T-cell and B-cell lymphopenia was present in PB pre-ART in HIV+ patients. CD4:CD8 and CD4 T- and B-cell PB subsets partly normalized compared to HC post-ART as viral load decreased. Strikingly in LN, ART led to a rapid decrease in interferon signaling pathways and an increase in Tfh, germinal center and IgD-CD27- B cells, consistent with histological findings of post-ART follicular hyperplasia. However, there was evidence of cTfh cells with decreased helper capacity and of limited B-cell receptor diversification post-ART. In conclusion, we found early signs of immune reconstitution, evidenced by a surge in LN germinal center cells, albeit limited in functionality, in HIV+ patients who initiate ART late in disease.

scholarly journals B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells

2011 ◽  
Vol 208 (7) ◽  
pp. 1377-1388 ◽  
Author(s):  
Sau K. Lee ◽  
Robert J. Rigby ◽  
Dimitra Zotos ◽  
Louis M. Tsai ◽  
Shimpei Kawamoto ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Antibody Responses ◽  
B Cell Differentiation ◽  
Tfh Cells ◽  
Follicular Helper ◽  
Microbial Infections

T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell–expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6+ T cells appear at the T–B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6+ PD-1hi T cells, which are found within the GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl-6+ T cells are necessary at B cell priming to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells.

scholarly journals Soluble CD40 ligand can replace the normal T cell-derived CD40 ligand signal to B cells in T cell-dependent activation.

1993 ◽  
Vol 177 (4) ◽  
pp. 1209-1213 ◽  
Author(s):  
P Lane ◽  
T Brocker ◽  
S Hubele ◽  
E Padovan ◽  
A Lanzavecchia ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cd40 Ligand ◽  
Thymidine Uptake ◽  
Soluble Cd40 Ligand ◽  
Cell Numbers ◽  
Modest Degree ◽  
Human And Mouse

We have constructed a soluble chimeric fusion protein between the mouse CD8 alpha chain and the mouse CD40 T cell ligand. This protein binds to both human and mouse B cells. By itself it induced a modest degree of B cell proliferation, but together with anti-immunoglobulin (anti-Ig) antibody it greatly stimulated B cell proliferation, as determined by both [3H]thymidine uptake and increase in cell numbers. These data are evidence that the CD40 ligand on T cells provides a signal that drives B cell proliferation. This signal is synergistic with that delivered by anti-Ig antibody.

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