Human Memory B Lymphocyte Subsets Fulfill Distinct Roles in the Anti-Polysaccharide and Anti-Protein Immune Response

Moens, Leen; Wuyts, Margareta; Meyts, Isabelle; Boeck, K. De; Bossuyt, Xavier

doi:10.4049/jimmunol.181.8.5306

Cited by 54 publications

(46 citation statements)

References 37 publications

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“…In contrast, we provide evidence that early changes in the phenotype of circulating B cells in alemtuzumab-treated patients correlated with the development of DSA posttransplantation. A previous report in patients with multiple sclerosis showed that even multiple doses of alemtuzumab failed to significantly decrease CD27 + memory B cell percentages 1 mo after administration (32) Abs against pneumococcal surface protein A, a T cell-dependent Ag (33). Similarly, the CD27 + B cell subset isolated from the peripheral blood of sensitized patients was able to produce alloantibodies in vitro (34).…”

Section: Discussionmentioning

confidence: 92%

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

Todeschini

Cortinovis

Perico

et al. 2013

The Journal of Immunology

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In this single-center matched-cohort study, we evaluated the phenotype of repopulating B cells and its correlation with donor-specific anti-HLA Ab development and long-term graft function in 16 renal transplant recipients and 32 age- and gender-matched controls induced with alemtuzumab or basiliximab (Bas)/low-dose rabbit anti-thymocyte globulin (rATG), respectively. Alemtuzumab, but not Bas/rATG, profoundly depleted peripheral B cells in the first 2 mo posttransplantation. Early posttransplant, naive B cells were significantly depleted, whereas Ag-experienced and memory B cells were partially spared. Transitional B cells transiently increased 2 mo posttransplant. At month 6 posttransplant, pregerminal center B cells emerged, a process promoted by increased BAFF serum levels. Thereafter, B cell counts increased progressively, mainly due to expansion of naive B cells. Conversely, Bas/rATG did not modify the B cell phenotype throughout the follow-up period. Alemtuzumab was associated with a higher incidence of de novo DSA compared with Bas/rATG. DSA development was predicted by changes in the B cell compartment and correlated with worse long-term graft function. Thus, alemtuzumab-induced B cell depletion/reconstitution may promote chronic humoral responses against the graft.

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Section: Discussionmentioning

confidence: 92%

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

Todeschini

Cortinovis

Perico

et al. 2013

The Journal of Immunology

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“…However, various studies have shown that PPS induce efficient activation of IgM + memory B cells (IgM + IgD + CD27 + ) and generation of long-lived plasma cells (CD38 + CD20 low ). This is accompanied by the generation and persistence of IgM and IgG antibodies against PPS [101][102][103][104][105][106][107][108]. IgM + memory B cells circulating in the blood are the peripheral correlates of the marginal zone B cells of the spleen.…”

Section: Immunogenicitymentioning

confidence: 99%

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

Falkenhorst

Remschmidt

Harder

et al. 2016

Bundesgesundheitsbl

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are members of the German Standing Committee on Vaccination (STIKO). Bundesgesundheitsblatt -Gesundheitsforschung -Gesundheitsschutz 12 · 2016 1624Tätigkeitsberichte Summary Background and objective The incidence of pneumococcal diseases among adults increases with age. Therefore, Germany's Standing Committee on Vaccination (Ständige Impfkommission, STIKO) has since 1998 recommended vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23) for all people aged ≥60 years. PPSV23 has been the only pneumococcal vaccine licensed for adults until few years ago. Universal pneumococcal vaccination of infants, using a conjugate vaccine, has been recommended by STIKO since 2006. Since then, pneumococcal serotypes contained in conjugate vaccines have declined among cases of pneumococcal disease not only in children, but -through herd protection -also in older adults. The 13-valent pneumococcal conjugate vaccine (PCV13), currently used for most infants in Germany, has now been approved for use in adults as well. Data on the efficacy of PCV13 against clinical endpoints in older adults was published in 2015. For that reason, STIKO investigated whether one of the two vaccines (or the combination of both) should be preferred in order to reduce the burden of pneumococcal diseases in older adults, and at what age the vaccine should be given. Efficacy against invasive pneumococcal diseasesPooled data from 4 randomised controlled trials (RCTs) of PPSV23 in older adults show an efficacy of 73 % against invasive pneumococcal disease (IPD) caused by any serotype (95 % confidence interval [CI], 10-92 %). The IPD cases in these studies were mostly caused by one of the 23 serotypes contained in the vaccine. The efficacy of PCV13 in older adults was investigated in one RCT. Efficacy against IPD by any serotype was 49 % (95 % CI, 21-67 %, modified-intention-to-treat analysis). Efficacy against IPD by the 13 serotypes contained in the vaccine (VT-IPD) was 76 % (95 % CI, 47-90 %). Efficacy against pneumococcal pneumoniaAfter exclusion of 2 RCTs with a high risk of bias, pooled efficacy of PPSV23 against pneumococcal pneumonia (PP) caused by any serotype in the remaining 2 RCTs was 64 % (95 % CI, 35-80 %). In the included observational studies, pooled efficacy ranged from 37 % to 53 %, with broadly overlapping CIs, depending on study type. The efficacy of PCV13 against PP caused by any serotype was 22 % (95 % CI, 2-39 %), and against VT-PP it was 38 % (95 % CI, 14-55 %). Anticipated epidemiological and health economic effectsThe above-mentioned studies do not provide clear evidence of a difference between the two vaccines regarding efficacy against clinical endpoints (IPD, PP) caused by the serotypes contained in the respective vaccine. In the 2015-'16 season, 70 % of IPD cases in people aged ≥60 years were caused by PPSV23 serotypes, but only 30 % by PCV13 serotypes. Because PPSV23 contains all the serotypes in PCV13 (except for serotype 6A), vaccination with PPSV23 confers broader serotype coverage and can thereby prevent ...

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“…Adoptive transfer of human lymphocytes was performed as previously reported (46). Four buffy coats were provided by the Blood Bank of Stanford University.…”

Section: Isolation Of B Cells By Rosette Formation and Purification Omentioning

confidence: 99%

Human Rotavirus-Specific IgM Memory B Cells Have Differential Cloning Efficiencies and Switch Capacities and Play a Role in Antiviral ImmunityIn Vivo

Narváez

Feng

Vásquez

et al. 2012

J Virol

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Protective immunity to rotavirus (RV) is primarily mediated by antibodies produced by RV-specific memory B cells (RV-mBc).Of note, most of these cells express IgM, but the function of this subset is poorly understood. Here, using limiting dilution assays of highly sort-purified human IgM ؉ mBc, we found that 62% and 21% of total (non-antigen-specific) IgM ؉ and RV-IgM ؉ mBc, respectively, switched in vitro to IgG production after polyclonal stimulation. Moreover, in these assays, the median cloning efficiencies of total IgM ؉ (17%) and RV-IgM ؉ (7%) mBc were lower than those of the corresponding switched (IgG ؉ IgA ؉ ) total (34%) and RV-mBc (17%), leading to an underestimate of their actual frequency. In order to evaluate the in vivo role of IgM ؉ RV-mBc in antiviral immunity, NOD/Shi-scid interleukin-2 receptor-deficient (IL-2R␥null ) immunodeficient mice were adoptively transferred highly purified human IgM ؉ mBc and infected with virulent murine rotavirus. These mice developed high titers of serum human RV-IgM and IgG and had significantly lower levels than control mice of both antigenemia and viremia. Finally, we determined that human RV-IgM ؉ mBc are phenotypically diverse and significantly enriched in the IgM hi IgD low subset. Thus, RV-IgM ؉ mBc are heterogeneous, occur more frequently than estimated by traditional limiting dilution analysis, have the capacity to switch Ig class in vitro as well as in vivo, and can mediate systemic antiviral immunity.

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Human Memory B Lymphocyte Subsets Fulfill Distinct Roles in the Anti-Polysaccharide and Anti-Protein Immune Response

Cited by 54 publications

References 37 publications

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

Human Rotavirus-Specific IgM Memory B Cells Have Differential Cloning Efficiencies and Switch Capacities and Play a Role in Antiviral ImmunityIn Vivo

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