scholarly journals A High Frequency of HIV-Specific Circulating Follicular Helper T Cells Is Associated with Preserved Memory B Cell Responses in HIV Controllers

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
M. Claireaux ◽  
M. Galperin ◽  
D. Benati ◽  
A. Nouël ◽  
M. Mukhopadhyay ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Helper T Cells ◽  
Memory B Cell ◽  
Cell Responses ◽  
Follicular Helper ◽  
Specific Igg ◽  
B Cell Responses ◽  
Controller Group ◽  
Hiv Controllers

ABSTRACT Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4 + T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet + ), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA − CXCR5 + CD4 + T cell population, proved more frequent in the controller group ( P = 0.002). The frequency of PD-1 expression in Tet + cTfh was increased in both groups (median, >75%) compared to total cTfh (<30%), but the intensity of PD-1 expression per cell remained higher in the treated patient group ( P = 0.02), pointing to the persistence of abnormal immune activation in treated patients. The function of cTfh, analyzed by the capacity to promote IgG secretion in cocultures with autologous memory B cells, did not show major differences between groups in terms of total IgG production but proved significantly more efficient in the controller group when measuring HIV-specific IgG production. The frequency of Tet + cTfh correlated with HIV-specific IgG production ( R = 0.71 for Gag-specific and R = 0.79 for Env-specific IgG, respectively). Taken together, our findings indicate that key cTfh-B cell interactions are preserved in controlled HIV infection, resulting in potent memory B cell responses that may play an underappreciated role in HIV control. IMPORTANCE The rare patients who spontaneously control HIV replication in the absence of therapy provide a unique model to identify determinants of an effective anti-HIV immune response. HIV controllers show signs of particularly efficient antiviral T cell responses, while their humoral response was until recently considered to play only a minor role in viral control. However, emerging evidence suggests that HIV controllers maintain a significant but “silent” antiviral memory B cell population that can be reactivated upon antigenic stimulation. We report that cTfh help likely contributes to the persistence of controller memory B cell responses, as the frequency of HIV-specific cTfh correlated with the induction of HIV-specific antibodies in functional assays. These findings suggest that T follicular help may contribute to HIV control and highlight the need for inducing such help in HIV vaccine strategies that aim at eliciting persistent B cell responses.

scholarly journals Antibody Avidity in Humoral Immune Responses in Bangladeshi Children and Adults following Administration of an Oral Killed Cholera Vaccine

2013 ◽  
Vol 20 (10) ◽  
pp. 1541-1548 ◽  
Author(s):  
Mohammad Murshid Alam ◽  
Daniel T. Leung ◽  
Marjahan Akhtar ◽  
Mohammad Nazim ◽  
Sarmin Akter ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
T Cell Responses ◽  
Memory B Cell ◽  
Antibody Avidity ◽  
Memory T Cell ◽  
Cell Responses ◽  
Specific Memory ◽  
Iga Antibodies ◽  
Specific Igg

ABSTRACTAntibody avidity for antigens following disease or vaccination increases with affinity maturation and somatic hypermutation. In this study, we followed children and adults in Bangladesh for 1 year following oral cholera vaccination and measured the avidity of antibodies to the T cell-dependent antigen cholera toxin B subunit (CTB) and the T cell-independent antigen lipopolysaccharide (LPS) in comparison with responses in other immunological measurements. Children produced CTB-specific IgG and IgA antibodies of high avidity following vaccination, which persisted for several months; the magnitudes of responses were comparable to those seen in adult vaccinees. The avidity of LPS-specific IgG and IgA antibodies in vaccinees increased significantly shortly after the second dose of vaccine but waned rapidly to baseline levels thereafter. CTB-specific memory B cells were present for only a short time following vaccination, and we did not find significant memory B cell responses to LPS in any age group. For older children, there was a significant correlation between CTB-specific memory T cell responses after the second dose of vaccine and CTB-specific IgG antibody avidity indices over the subsequent year. These findings suggest that vaccination induces a longer-lasting increase in the avidity of antibodies to a T cell-dependent antigen than is measured by a memory B cell response to that antigen and that early memory T cell responses correlate well with the subsequent development of higher-avidity antibodies.

scholarly journals Study of Avidity of Antigen-Specific Antibody as a Means of Understanding Development of Long-Term Immunological Memory after Vibrio cholerae O1 Infection

2012 ◽  
Vol 20 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Mohammad Murshid Alam ◽  
Mohammad Arifuzzaman ◽  
Shaikh Meshbahuddin Ahmad ◽  
M. Ismail Hosen ◽  
Mohammad Arif Rahman ◽  
...  
Keyword(s):  
B Cell ◽  
Vibrio Cholerae ◽  
Memory B Cell ◽  
Content Type ◽  
Cell Responses ◽  
Specific Memory ◽  
Iga Antibodies ◽  
Specific Igg ◽  
B Cell Responses

ABSTRACTThe avidity of antibodies to specific antigens and the relationship of avidity to memory B cell responses to these antigens have not been studied in patients with cholera or those receiving oral cholera vaccines. We measured the avidity of antibodies to cholera toxin B subunit (CTB) andVibrio choleraeO1 lipopolysaccharide (LPS) in Bangladeshi adult cholera patients (n= 30), as well as vaccinees (n= 30) after administration of two doses of a killed oral cholera vaccine. We assessed antibody and memory B cell responses at the acute stage in patients or prior to vaccination in vaccinees and then in follow-up over a year. Both patients and vaccinees mounted CTB-specific IgG and IgA antibodies of high avidity. Patients showed longer persistence of these antibodies than vaccinees, with persistence lasting in patients up to day 270 to 360. The avidity of LPS-specific IgG and IgA antibodies in patients remained elevated up to 180 days of follow-up. Vaccinees mounted highly avid LPS-specific antibodies at day 17 (3 days after the second dose of vaccine), but the avidity waned rapidly to baseline by 30 days. We examined the correlation between antigen-specific memory B cell responses and avidity indices for both antigens. We found that numbers of CTB- and LPS-specific memory B cells significantly correlated with the avidity indices of the corresponding antibodies (P< 0.05; Spearman'sρ= 0.28 to 0.45). These findings suggest that antibody avidity after infection and immunization is a good correlate of the development and maintenance of memory B cell responses toVibrio choleraeO1 antigens.

scholarly journals Cognate T and B cell interaction and association of follicular helper T cells with B cell responses in Vibrio cholerae O1 infected Bangladeshi adults

2019 ◽  
Vol 21 (3-4) ◽  
pp. 176-183 ◽  
Author(s):  
Rasheduzzaman Rashu ◽  
Taufiqur Rahman Bhuiyan ◽  
Mohammad Rubel Hoq ◽  
Lazina Hossain ◽  
Anik Paul ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Cell Interaction ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Cell Responses ◽  
Follicular Helper ◽  
Vibrio Cholerae O1 ◽  
B Cell Responses

scholarly journals Memory T-Cell Responses to Vibrio cholerae O1 Infection

2009 ◽  
Vol 77 (11) ◽  
pp. 5090-5096 ◽  
Author(s):  
Ana A. Weil ◽  
Mohammad Arifuzzaman ◽  
Taufiqur R. Bhuiyan ◽  
Regina C. LaRocque ◽  
Aaron M. Harris ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Protective Immunity ◽  
T Cell Responses ◽  
Memory B Cell ◽  
Memory T Cell ◽  
Cell Responses ◽  
B Cell Responses

ABSTRACTVibrio choleraeO1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses toV. choleraeinfection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severeV. choleraeinfection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses usingV. choleraeantigens, including the toxin-coregulated pilus (TcpA), aV. choleraemembrane preparation, and theV. choleraecytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses toV. choleraeantigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to otherV. choleraeantigens.

scholarly journals Persistence of antibody and T cell responses to the Sinopharm/BBIBP-CorV vaccine in Sri Lankan individuals

2021 ◽  
Author(s):  
Chandima Jeewandara ◽  
Inoka Aberathna ◽  
Pradeep Pushpakumara ◽  
Achala Kamaladasa ◽  
Dinuka Guruge ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
B Cell ◽  
Severe Disease ◽  
Age Groups ◽  
T Cell Responses ◽  
Sri Lankan ◽  
Memory B Cell ◽  
Cell Responses ◽  
B Cell Responses

Background: To determine the kinetics and persistence of immune responses following the Sinopharm/BBIBP-CorV, we investigated immune responses in a cohort of Sri Lankan individuals. Methods: SARS-CoV-2 specific total antibodies were measured in 20-to-39 year (n=61), 40-to-59-year and those >60 years of age (n=22) by ELISA, 12 weeks after the second dose of the vaccine. ACE2 receptor blocking antibodies (ACE2R-Ab), antibodies to the receptor binding domain (RBD) of the ancestral virus (WT) and variants of concern, were measured in a sub cohort. T cell responses and memory B cell responses were assessed by ELISpot assays. Results: 193/203 (95.07%) of individuals had detectable SARS-CoV-2 specific total antibodies, while 67/110 (60.9%) had ACE2R-Ab. 14.3% to 16.7% individuals in the 20 to 39 age groups had detectable antibodies to the RBD of the WT and VOC, while the positivity rates of those >60 years of age was <10%. 14/49 (28.6%) had IFNγ ELISpot responses to overlapping peptides of the spike protein, while memory B cell responses were detected in 9/20 to the S1 recombinant protein. The total antibody levels and ACE2R-Ab declined after 2 to 12 weeks from the second dose, while ex vivo T cell responses remained unchanged. The decline in ACE2R-Ab levels was significant among the 40 to 59 (p=0.0007) and ≥60 (p=0.005) age groups. Conclusions: Antibody responses declined in all age groups, especially in those >60 years, while T cell responses persisted. The effect of waning of immunity on hospitalization and severe disease should be assessed by long term efficacy studies.

scholarly journals Impaired Memory B-Cell Response to Influenza Immunization in Patients With Common Variable Immunodeficiency (CVID)

2021 ◽  
Vol 6 (2) ◽  
pp. 105-118
Author(s):  
Wei Zhan ◽  
Todd Hatchette ◽  
Fengyun Yue ◽  
Jun Liu ◽  
Haihan Song ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Healthy Controls ◽  
Memory B Cell ◽  
Post Vaccination ◽  
Cell Responses ◽  
Specific Memory ◽  
Specific Igg ◽  
B Cell Responses

Background: Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency characterized by low serum antibody levels and recurrent infections. The cellular response to immunization in patients with CVID has not been fully investigated. In this study, we aimed to characterize vaccination-induced influenza-specific memory B-cell responses in CVID. Methods: Eleven individuals affected with CVID and 9 unaffected control individuals were immunized with the 2010-2011 non-adjuvanted seasonal influenza vaccine. Blood samples were collected on the day of vaccination and at week 8 and week 16 after vaccination, and PBMCs were immunophenotyped by flow cytometry. Influenza specific serology was determined using hemagglutination inhibition and microneutralization against vaccine antigens. Influenza-specific memory B-cell responses were determined by ELISpot.  Results: Individuals with CVID showed wide variability in the frequency of CD19+ B cells in blood. The CVID group had significantly reduced frequencies of CD19+CD27+ memory B cells. Frequencies of circulating T follicular helper (CD4+CXCR5+) cells were similar between those with CVID and healthy controls. In terms of serology, compared to healthy controls, the CVID group overall showed significantly reduced boosting to vaccine antigens by hemagglutination inhibition and microneutralization assays at 8 weeks compared to controls and failed to maintain responses by 16 weeks compared to controls, resulting in a post-vaccination geometric mean titer (GMT) ≥ 40 to strain A/H1N1 in only 27% at 8 weeks, and 22% at 12 weeks for patients with CVID vs 78% and 75%, respectively for healthy controls. In addition, there was a GMT ≥ 40 to A/H3N2 in only 9% at 8 weeks and 22% at 12 weeks for patients with CVID vs 56% and 50%, respectively for healthy controls. Healthy participants showed significant increases in flu-specific IgM-secreting memory B cells after vaccination, whereas patients with CVID showed non-significant mild increases. Before vaccination, patients with CVID had significantly lower frequencies of background level influenza-specific IgG and IgA memory B cells. Half of the patients with CVID showed an increase in influenza-specific IgG-secreting memory B cells post vaccination, whereas the other half showed none. All control participants exhibited an increase in influenza-specific IgG-secreting B cells. None of the patients with CVID developed influenza-specific IgA memory B-cell response post vaccination, compared to 5/8 in healthy controls. At week 16, the frequency of influenza-specific memory B-cell responses decayed but to non-zero baseline in healthy controls and to zero baseline in patients with CVID.  Conclusions: Together, these data demonstrate that patients with CVID respond heterogeneously, but as a group poorly, to non-adjuvanted influenza vaccine, with a subgroup unable to generate influenza-specific memory B-cell responses. No patient with CVID was able to maintain memory response for prolonged periods. Together, our results suggest a defect in Ig class switching and memory B-cell maintenance in patients with CVID during a de novo vaccine immune response.

scholarly journals Antigen-Specific Memory B-Cell Responses to Vibrio cholerae O1 Infection in Bangladesh

2009 ◽  
Vol 77 (9) ◽  
pp. 3850-3856 ◽  
Author(s):  
Aaron M. Harris ◽  
M. Saruar Bhuiyan ◽  
Fahima Chowdhury ◽  
Ashraful I. Khan ◽  
Azim Hossain ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Vibrio Cholerae ◽  
Cell Response ◽  
Memory B Cells ◽  
Protein Antigens ◽  
Memory B Cell ◽  
Cell Responses ◽  
Specific Igg ◽  
B Cell Responses

ABSTRACT Cholera, caused by Vibrio cholerae, is a noninvasive dehydrating enteric disease with a high mortality rate if untreated. Infection with V. cholerae elicits long-term protection against subsequent disease in countries where the disease is endemic. Although the mechanism of this protective immunity is unknown, it has been hypothesized that a protective mucosal response to V. cholerae infection may be mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue. To characterize memory B-cell responses to cholera, we enrolled a cohort of 39 hospitalized patients with culture-confirmed cholera and evaluated their immunologic responses at frequent intervals over the subsequent 1 year. Memory B cells to cholera antigens, including lipopolysaccharide (LPS), and the protein antigens cholera toxin B subunit (CTB) and toxin-coregulated pilus major subunit A (TcpA) were enumerated using a method of polyclonal stimulation of peripheral blood mononuclear cells followed by a standard enzyme-linked immunospot procedure. All patients demonstrated CTB, TcpA, and LPS-specific immunoglobulin G (IgG)and IgA memory responses by day 90. In addition, these memory B-cell responses persisted up to 1 year, substantially longer than other traditional immunologic markers of infection with V. cholerae. While the magnitude of the LPS-specific IgG memory B-cell response waned at 1 year, CTB- and TcpA-specific IgG memory B cells remained significantly elevated at 1 year after infection, suggesting that T-cell help may result in a more durable memory B-cell response to V. cholerae protein antigens. Such memory B cells could mediate anamnestic responses on reexposure to V. cholerae.

Author response for "Dysregulation in B cell responses and T follicular helper cell function in ADA2 deficiency patients"

2020 ◽  
Author(s):  
Francesca Schena ◽  
Federica Penco ◽  
Stefano Volpi ◽  
Claudia Pastorino ◽  
Roberta Caorsi ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Function ◽  
Author Response ◽  
Helper Cell ◽  
Cell Responses ◽  
Follicular Helper ◽  
T Follicular Helper Cell ◽  
B Cell Responses
Sign in / Sign up

Export Citation Format

Share Document