Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

Winklmeier, Stephan; Eisenhut, Katharina; Taskin, Damla; Rübsamen, Heike; Gerhards, Ramona; Schneider, Celine; Wratil, Paul R.; Stern, Marcel; Eichhorn, Peter; Keppler, Oliver T.; Klein, Matthias; Mader, Simone; Kümpfel, Tania; Meinl, Edgar

doi:10.1016/j.isci.2021.103659

Cited by 18 publications

(11 citation statements)

References 75 publications

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“…In agreement with those findings, severe COVID 19 induces an exhaustion phenotype on S1-specific IgG + MBCs compared with healthy and recovered individuals ( 34 ). Although SARS-CoV-2-specific antibodies tend to wane over time, the persistence of MBC could supply its lost ( 35 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

et al. 2022

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BackgroundThe COVID-19 pandemic remains a global health problem. As in other viral infections, the humoral immune response against SARS-CoV-2 is thought to be crucial for controlling the infection. However, the dynamic of B cells in the clinical spectrum of this disease is still controversial. This study aimed to characterize B cell subsets and neutralizing responses in COVID-19 patients according to disease severity through a one-month follow-up.MethodsA cohort of 71 individuals with SARS-CoV-2 infection confirmed by RT-PCR were recruited and classified into four groups: i) asymptomatic; ii) symptomatic outpatients; iii) hospitalized in ward, and iv) intensive care unit patients (ICU). Samples were taken at days 0 (inclusion to the study), 7 and 30. B cell subsets and neutralizing antibodies were assessed using multiparametric flow cytometry and plaque reduction neutralization, respectively.ResultsOlder age, male gender and body mass index over 25 were common factors among hospitalized and ICU patients, compared to those with milder clinical presentations. In addition, those requiring hospitalization had more comorbidities. A significant increase in the frequencies of CD19+ cells at day 0 was observed in hospitalized and ICU patients compared to asymptomatic and symptomatic groups. Likewise, the frequency of plasmablasts was significantly increased at the first sample in the ICU group compared to the asymptomatic group, but then waned over time. The frequency of naïve B cells decreased at days 7 and 30 compared to day 0 in hospitalized and ICU patients. The neutralizing antibody titers were higher as the severity of COVID-19 increased; in asymptomatic individuals, it was strongly correlated with the percentage of IgM+ switched memory B cells, and a moderate correlation was found with plasmablasts.ConclusionThe humoral immune response is variable among SARS-CoV-2 infected people depending on the severity and time of clinical evolution. In severe COVID-19 patients, a higher plasmablast frequency and neutralizing antibody response were observed, suggesting that, despite having a robust humoral immunity, this response could be late, having a low impact on disease outcome.

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Section: Discussionmentioning

confidence: 99%

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

et al. 2022

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“…vivax subjects who had recovered from infection for 1–3 months (RCs) and harbored cross-reactive inhibitory antibodies in circulating blood (RC01, RC02, RC03, RC04 and RC06) were used to detect broad MBC responses to DBL-TH variants. PBMCs (1 x 10 6 ) from these RC patients (n = 5) and HCs (n = 4) were transferred into 24-well plates containing 1 mL of culture medium (RPMI + 10% FCS) and subsequently differentiated into antibody-secreting cells (ASCs) with stimulation of R848 (2.5 μg/mL; Invivogen, San Diego, CA, USA) and IL-2 (1,000 IU/mL; Peprotech, Rocky Hill, NJ, USA) at 37°C, 5% CO 2 for 11 days, as previously described [ 23 ]. In this culture system memory B cells differentiated into ASCs [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Cross-reactive inhibitory antibody and memory B cell responses to variant strains of Duffy binding protein II at post-Plasmodium vivax infection

et al. 2022

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Duffy binding protein region II (DBPII) is considered a strong potential vaccine candidate of blood-stage P. vivax. However, the highly polymorphic nature of this protein often misdirects immune responses, leading them to be strain-specific. Details of cross-reactive humoral immunity to DBPII variants have therefore become an important focus for the development of broadly protective vaccines. Here, cross-reactive humoral immunity against a panel of Thai DBPII variants (DBL-THs) was demonstrated in immunized BALB/c mice and P. vivax patients, by in vitro erythrocyte-binding inhibition assay. Sera from immunized animals showed both strain-transcending (anti-DBL-TH2 and -TH4) and strain-specific (anti-DBL-TH5, -TH6 and -TH9) binding to DBL-TH variants. Using anti-DBL-TH sera at 50% inhibitory concentration (IC50) of the homologous strain, anti-DBL-TH2 sera showed cross inhibition to heterologous DBL-TH strains, whereas anti-DBL-TH5 sera exhibited only strain-specific inhibition. In P. vivax patients, 6 of 15 subjects produced and maintained cross-reactive anti-DBL-TH inhibitory antibodies through the 1-year post-infection timepoint. Cross-reactive memory B cell (MBC) responses to DBL-TH variants were analyzed in subjects recovered from P. vivax infection (RC). The plasma samples from 5 RC subjects showed broad inhibition. However, MBC-derived antibodies of these patients did not reveal cross-inhibition. Altogether, broadly anti-DBP variant inhibitory antibodies developed and persisted in P. vivax infections. However, the presence of cross-reactive anti-DBL-TH inhibitory function post-infection was not related with MBC responses to these variants. More detailed investigation of long-lasting, broadly protective antibodies to DBPII will guide the design of vivax malaria vaccines.

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“…RBD-specific MBCs that have undergone SHM in GCs and produce high affinity nAbs have frequencies that remain unchanged or even rise 6 months after infection ( 75 , 76 ). Moreover, a recent study showed an encouraging discovery that functional IgG MBCs persist after 5-8 months in infected patients, while the level of serum SARS-CoV-2 specific IgG is eventually lost ( 77 ). This might suggest that the level of MBCs is more sensitive for detection of previous infection and prediction of long-term protection.…”

Section: B Cells Response In Covid-19 Infectionmentioning

confidence: 99%

The role of B cells in COVID-19 infection and vaccination

et al. 2022

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B cells secrete antibodies and mediate the humoral immune response, making them extremely important in protective immunity against SARS-CoV-2, which caused the coronavirus disease 2019 (COVID-19) pandemic. In this review, we summarize the positive function and pathological response of B cells in SARS-CoV-2 infection and re-infection. Then, we structure the immunity responses that B cells mediated in peripheral tissues. Furthermore, we discuss the role of B cells during vaccination including the effectiveness of antibodies and memory B cells, viral evolution mechanisms, and future vaccine development. This review might help medical workers and researchers to have a better understanding of the interaction between B cells and SARS-CoV-2 and broaden their vision for future investigations.

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Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG

Cited by 18 publications

References 75 publications

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

Cross-reactive inhibitory antibody and memory B cell responses to variant strains of Duffy binding protein II at post-Plasmodium vivax infection

The role of B cells in COVID-19 infection and vaccination

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