Splenectomized Patients Have Reduced CD27+ Memory B Cells but Protective Antibody Responses to Pneumococcal Vaccination.

Abstract Introduction : Splenectomized patients are thought to have poor antibody responses to polyvalent non-conjugate pneumococcal vaccination. Recent studies found that these patients have decreased circulating CD27+ (memory) B cells, suggesting the possibility of a specific defect in splenectomized patients’ humoral immunity. In this study we sought to verify this reduction and ascertain whether it correlates with inadequate antibody production. Thus, we enumerated peripheral blood CD27+ B cells in splenectomized patients and non-splenectomized controls, administered a polyvalent non-conjugate pneumococcal vaccine, and compared their IgG antibody titers to all 23 serotypes before and 4 to 6 weeks after immunization. Participants : 31 participants were enrolled: 21 splenectomized patients (6 male, 15 female; age: 10–80 years, mean: 47.3) and 10 non-splenectomized controls (2 male, 8 female; age: 26–64 years, mean: 37.5). Indications for splenectomy included ITP (17), spherocytosis (2), hemolytic anemia (1), and thrombocytopenia-absent radii syndrome (1). No patients received pneumococcal vaccination within 2 years, or IVIG, Rituxan or immunosuppressive therapy within 6 months of enrollment. Time since splenectomy ranged from 6 months to 50 years (mean: 12.5). 17 patients received at least one prior pneumococcal immunization, from 3 to 22 years previously (mean: 8.0). No controls formerly received a pneumococcal vaccination. Results : B Cell Enumeration: Compared to the 10 controls, the 21 splenectomized patients had a greater percentage of circulating B cells (patients: 12.05% ± 7.61; controls: 7.99% ± 2.92; ρ = 0.042), but a significantly reduced CD27+ B cell component (patients: 12.38% ± 8.48; controls: 40.46% ± 18.68; ρ = 0.001). This reduction was not specific to either of the CD27+ B cell populations (IgM+IgD+CD27+: patients: 31.64% ± 19.72; controls: 44.58% ± 16.01; ρ = 0.081. IgM−IgD−CD27+: patients: 52.05 ± 23.71; controls: 48.08% ± 13.89; ρ = 0.628.) Antibody Analysis: Antibody responses to pneumococcal vaccination did not differ significantly between splenectomized patients and non-splenectomized controls. 9 of 13 splenectomized patients and 9 of 10 controls achieved protection to immunization (χ2 = 1.433; ρ = 0.339), defined as a post-vaccination IgG titer ≥ 1.3 μg/ml or a post:pre-vaccination titer ratio ≥ 4, in at least 70% of the serotypes tested (~16 of 23 serotypes). When comparing the mean number of serotypes to which each cohort achieved protection, splenectomized patients and controls mounted statistically similar responses, at 17 and 20 serotypes, respectively (ρ = 0.134). Furthermore, the geometric means of each cohort’s post-vaccination IgG titers did not differ significantly in 22 of the 23 serotypes. Conclusion : Splenectomized patients had a significant reduction in their circulating CD27+ B cells. This decrease did not correlate with an impaired antibody response to (re-)immunization with a polyvalent non-conjugate pneumococcal vaccine however, as splenectomized patients and non-splenectomized controls achieved comparable protection and produced similar IgG responses to vaccination. For ITP patients and others who have undergone splenectomy, our data indicates that a pneumococcal vaccine can be effectively administered after splenectomy, if needed.

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Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

10.1101/2020.09.04.20187724 ◽

2020 ◽

Cited By ~ 1

Author(s):

Krista L Newell ◽

Deanna C Clemmer ◽

Justin B Cox ◽

Yetunde I Kayode ◽

Victoria Zoccoli-Rodriguez ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Respiratory Illness ◽

Significant Negative Correlation ◽

Memory B Cells ◽

Antibody Responses ◽

Symptom Duration ◽

Memory B Cell ◽

Duration Of Symptoms

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD). IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over time. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells play an important role in SARS-CoV-2 immunity.

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Critical requirement for BCR, BAFF, and BAFFR in memory B cell survival

Journal of Experimental Medicine ◽

10.1084/jem.20191393 ◽

2020 ◽

Vol 218 (2) ◽

Cited By ~ 1

Author(s):

Jennifer Müller-Winkler ◽

Richard Mitter ◽

Julie C.F. Rappe ◽

Lesley Vanes ◽

Edina Schweighoffer ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Memory B Cells ◽

Antibody Responses ◽

B Cell Antigen Receptor ◽

Critical Part ◽

Genetic Ablation ◽

B Cell Survival ◽

Critical Requirement ◽

Rapid Antibody

Memory B cells (MBCs) are long-lived cells that form a critical part of immunological memory, providing rapid antibody responses to recurring infections. However, very little is known about signals controlling MBC survival. Previous work has shown that antigen is not required for MBC survival, but a requirement for the B cell antigen receptor (BCR) has not been tested. Other studies have shown that, unlike naive B cells, MBCs do not express BAFFR and their survival is independent of BAFF, the ligand for BAFFR. Here, using inducible genetic ablation, we show that survival of MBCs is critically dependent on the BCR and on signaling through the associated CD79A protein. Unexpectedly, we found that MBCs express BAFFR and that their survival requires BAFF and BAFFR; hence, loss of BAFF or BAFFR impairs recall responses. Finally, we show that MBC survival requires IKK2, a kinase that transduces BAFFR signals. Thus, MBC survival is critically dependent on signaling from BCR and BAFFR.

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Reduced Circulating Memory B-Cells Account for Humoral Immune Defects in Multiple Myeloma, Associated with Infective Risk and Poor Vaccination Responses

Blood ◽

10.1182/blood.v124.21.3393.3393 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3393-3393

Author(s):

Jonathan Carmichael ◽

Clive R Carter ◽

Christopher Parrish ◽

Charlotte Kallmeyer ◽

Sylvia Feyler ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Bacterial Infections ◽

Memory B Cells ◽

Antibody Responses ◽

Progressive Reduction ◽

Cell Numbers ◽

Humoral Immune ◽

Transitional B Cells ◽

B Cell Subsets

Abstract Multiple myeloma (MM) is characterized by an increased risk of infection due to the immunosuppressive effect of the disease and conjointly of therapy. Furthermore, there is impaired responses to vaccination to counter the infection risk. The factors that underpin defective B-cell homeostasis and effective humoral immunity are not clear, nor are the extent of the defects. Also, the level of impaired humoral immunity in MGUS is not fully understood. The aim of this study was to delineate the circulating B-cell populations and recall antibody responses in patients with MGUS & MM, compared to age-matched controls, correlating with the responsiveness to vaccinations, incidence of infective complications and concomitant therapy. We performed comprehensive B-cell immunophenotyping by multi-parameter flow cytometry of peripheral blood samples from patients with MGUS (n=16), asymptomatic MM (n=18) and MM (n=108) with a median age of 63 years (range 38-94) comparing them to age-matched controls (n=9). B-cell subsets included naïve (CD19+CD27-), memory (CD19+CD27+; non-switch CD19+IgD+CD27+, switch CD19+IgD-CD27+), transitional (CD19+CD27-CD24hiCD38hi) & regulatory (CD19+CD27+CD24hi) B-cells. Serum uninvolved total IgG, IgM & IgA levels along with vaccine-specific antibody responses were analysed. There is a progressive decrease in the uninvolved immunoglobulin classes with significant reduction in total IgA (p=0.006) and IgM levels (p=0.007) in aMM/MM compared to MGUS & control (Figure 1). When anti-pneumococcal antibodies were measured, only 30% of aMM/MM patients had adequate protective levels compared to 79% of age-matched controls, with 40% of aMM/MM patients with inadequate levels experiencing recurrent respiratory tract infections compared to 25% of aMM/MM patients with adequate proactive antibodies. Patients with MGUS, aMM and MM have lower total B-cell numbers compared to controls (1-way ANOVA p=0.004; Figure 1). The reduction in B-cell numbers were primarily the consequence of reduced memory B-cells (percentage and absolute 1-way ANOVA p<0.0001), noted in both MGUS and aMM/MM but a progressive reduction with increasing disease activity (MGUS>aMM>MM). Furthermore, a correlation with total IgG levels & memory B-cell numbers is evident (r2=-0.053) & progressive reduction in memory B-cell numbers is seen with advancing cycles of therapy. The ratio of switch:non-switch memory B-cells is unaltered (control 1.05, MGUS 0.53, aMM 1.41 & MM 1.49; 1-way ANOVA p=ns). Conversely, there is a compensatory increase in the percentage of transitional B-cells when increasing disease stage is compared to controls (control 7.38% (95%ci 4.9,9.9) vs MGUS 14.0% (95%ci 7.4, 20.7) vs aMM 14.95% (95%ci 8, 21.9); 1-way ANOVA p<0.001) but a reduction is noted in MM (5.82%, 95%ci 4.5,7.2; p<0.0001), primarily being driven by sequential lines of therapy. As a consequence, the ratio of Memory:transitional B-cells is significantly reduced in aMM/MM compared to MGUS & controls (control 10.35, MGUS 20.46, aMM 7.74 & MM 4.57; 1-way ANOVA p=0.006), associated with increasing incidence of bacterial infections. A non-significant correlation is seen between transitional B-cells and total uninvolved immunoglobulin levels and with recall responses to vaccinations. There is a progressive decrease in the CD19+CD27+CD24hi B-cell subset between control and plasma cell dyscrasias (control 20.4% (95%ci 15.5,25.2), MGUS 14.0% (95%ci 7.4, 20.7), aMM 14.95% (95%ci 8, 21.9) & MM 5.82%, 95%ci 4.5,7.2; p<0.0001), primarily being driven by sequential lines of therapy and associated with increased incidence of infection. This study illustrates that patients with myeloma demonstrate reduced total circulating B-cells primarily as a consequence of reduced memory B-cells, associated with reduced immunoglobulin and recall antibody responses. This is associated with increased incidence of bacterial infections and is worsened by sequential exposure to lymphodepleting therapies. Of particular importance is the identified aberration in B-cell subsets seen in MGUS compared with age-matched control, indicative of humoral immune dysregulation highlighting that MGUS may not be an immunologically inert disorder. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Antiviral Antibodies Are Necessary for Control of Simian Immunodeficiency Virus Replication

Journal of Virology ◽

10.1128/jvi.02444-06 ◽

2007 ◽

Vol 81 (10) ◽

pp. 5024-5035 ◽

Cited By ~ 61

Author(s):

Christopher J. Miller ◽

Meritxell Genescà ◽

Kristina Abel ◽

David Montefiori ◽

Donald Forthal ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Simian Immunodeficiency Virus ◽

Early Time ◽

Antibody Responses ◽

Effective Control ◽

Igg Antibody ◽

Immunodeficiency Virus ◽

Antiviral Antibody ◽

Anti Cd20

ABSTRACT To better define the role of B cells in the control of pathogenic simian immunodeficiency virus (SIV) replication, six rhesus monkeys were depleted of B cells by intravenous infusion of rituximab (anti-CD20) 28 days and 7 days before intravaginal SIVmac239 inoculation and every 21 days thereafter until AIDS developed. Although the blood and tissues were similarly depleted of B cells, anti-SIV immunoglobulin G (IgG) antibody responses were completely blocked in only three of the six animals. In all six animals, levels of viral RNA (vRNA) in plasma peaked at 2 weeks and declined by 4 weeks postinoculation (PI). However, the three animals prevented from making an anti-SIV antibody response had significantly higher plasma vRNA levels through 12 weeks PI (P = 0.012). The remaining three B-cell-depleted animals made moderate anti-SIV IgG antibody responses, maintained moderate plasma SIV loads, and showed an expected rate of disease progression, surviving to 24 weeks PI without developing AIDS. In contrast, all three of the B-cell-depleted animals prevented from making anti-SIV IgG responses developed AIDS by 16 weeks PI (P = 0.0001). These observations indicate that antiviral antibody responses are critical in maintaining effective control of SIV replication at early time points postinfection.

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Serotype-Specific and Age-Dependent Generation of Pneumococcal Polysaccharide-Specific Memory B-Cell and Antibody Responses to Immunization with a Pneumococcal Conjugate Vaccine

Clinical and Vaccine Immunology ◽

10.1128/cvi.00336-07 ◽

2007 ◽

Vol 15 (2) ◽

pp. 182-193 ◽

Cited By ~ 38

Author(s):

Elizabeth A. Clutterbuck ◽

Sarah Oh ◽

Mainga Hamaluba ◽

Sharon Westcar ◽

Peter C. L. Beverley ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Plasma Cells ◽

Memory B Cells ◽

Antibody Responses ◽

Memory B Cell ◽

Cell Responses ◽

Specific Memory

ABSTRACT Glycoconjugate vaccines have dramatically reduced the incidence of encapsulated bacterial diseases in toddlers under 2 years of age, but vaccine-induced antibody levels in this age group wane rapidly. We immunized adults and 12-month-old toddlers with heptavalent pneumococcal conjugate vaccine to determine differences in B-cell and antibody responses. The adults and 12-month-old toddlers received a pneumococcal conjugate vaccine. The toddlers received a second dose at 14 months of age. The frequencies of diphtheria toxoid and serotype 4, 14, and 23F polysaccharide-specific plasma cells and memory B cells were determined by enzyme-linked immunospot assay. The toddlers had no preexisting polysaccharide-specific memory B cells or serum immunoglobulin G (IgG) antibody but had good diphtheria toxoid-specific memory responses. The frequencies of plasma cells and memory B cells increased by day 7 (P < 0.0001) in the adults and the toddlers following a single dose of conjugate, but the polysaccharide responses were significantly lower in the toddlers than in the adults (P = 0.009 to <0.001). IgM dominated the toddler antibody responses, and class switching to the IgG was serotype dependent. A second dose of vaccine enhanced the antibody and memory B-cell responses in the toddlers but not the ex vivo plasma cell responses. Two doses of pneumococcal conjugate vaccine are required in toddlers to generate memory B-cell frequencies and antibody class switching for each pneumococcal polysaccharide equivalent to that seen in adults.

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CD4+T Cells Promote Antibody Production but Not Sustained Affinity Maturation during Borrelia burgdorferi Infection

Infection and Immunity ◽

10.1128/iai.02471-14 ◽

2014 ◽

Vol 83 (1) ◽

pp. 48-56 ◽

Cited By ~ 18

Author(s):

Rebecca A. Elsner ◽

Christine J. Hastey ◽

Nicole Baumgarth

Keyword(s):

T Cells ◽

B Cells ◽

B Cell ◽

Cd4 T Cells ◽

Plasma Cells ◽

Affinity Maturation ◽

Memory B Cells ◽

Antibody Responses ◽

Content Type ◽

High Affinity

CD4 T cells are crucial for enhancing B cell-mediated immunity, supporting the induction of high-affinity, class-switched antibody responses, long-lived plasma cells, and memory B cells. Previous studies showed that the immune response toBorrelia burgdorferiappears to lack robust T-dependent B cell responses, as neither long-lived plasma cells nor memory B cells form for months after infection, and nonswitched IgM antibodies are produced continuously during this chronic disease. These data prompted us to evaluate the induction and functionality ofB. burgdorferiinfection-induced CD4 TFHcells. We report that CD4 T cells were effectively primed and TFHcells induced afterB. burgdorferiinfection. These CD4 T cells contributed to the control ofB. burgdorferiburden and supported the induction ofB. burgdorferi-specific IgG responses. However, while affinity maturation of antibodies against a prototypic T-dependentB. burgdorferiprotein, Arthritis-related protein (Arp), were initiated, these increases were reversed later, coinciding with the previously observed involution of germinal centers. The cessation of affinity maturation was not due to the appearance of inhibitory or exhausted CD4 T cells or a strong induction of regulatory T cells.In vitroT-B cocultures demonstrated that T cells isolated fromB. burgdorferi-infected but notB. burgdorferi-immunized mice supported the rapid differentiation of B cells into antibody-secreting plasma cells rather than continued proliferation, mirroring the induction of rapid short-lived instead of long-lived T-dependent antibody responsesin vivo. The data further suggest thatB. burgdorferiinfection drives the humoral response away from protective, high-affinity, and long-lived antibody responses and toward the rapid induction of strongly induced, short-lived antibodies of limited efficacy.

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Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals

Journal of Experimental Medicine ◽

10.1084/jem.20072683 ◽

2008 ◽

Vol 205 (8) ◽

pp. 1797-1805 ◽

Cited By ~ 540

Author(s):

Susan Moir ◽

Jason Ho ◽

Angela Malaspina ◽

Wei Wang ◽

Angela C. DiPoto ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Memory B Cells ◽

Antibody Responses ◽

Cell Subpopulation ◽

Cell Phenotype ◽

Inhibitory Receptors ◽

Memory B Cell ◽

Cell Exhaustion ◽

High Level

Human immunodeficiency virus (HIV) disease leads to impaired B cell and antibody responses through mechanisms that remain poorly defined. A unique memory B cell subpopulation (CD20hi/CD27lo/CD21lo) in human tonsillar tissues was recently defined by the expression of the inhibitory receptor Fc-receptor-like-4 (FCRL4). In this study, we describe a similar B cell subpopulation in the blood of HIV-viremic individuals. FCRL4 expression was increased on B cells of HIV-viremic compared with HIV-aviremic and HIV-negative individuals. It was enriched on B cells with a tissuelike memory phenotype (CD20hi/CD27−/CD21lo) when compared with B cells with a classical memory (CD27+) or naive (CD27−/CD21hi) B cell phenotype. Tissuelike memory B cells expressed patterns of homing and inhibitory receptors similar to those described for antigen-specific T cell exhaustion. The tissuelike memory B cells proliferated poorly in response to B cell stimuli, which is consistent with high-level expression of multiple inhibitory receptors. Immunoglobulin diversities and replication histories were lower in tissuelike, compared with classical, memory B cells, which is consistent with premature exhaustion. Strikingly, HIV-specific responses were enriched in these exhausted tissuelike memory B cells, whereas total immunoglobulin and influenza-specific responses were enriched in classical memory B cells. These data suggest that HIV-associated premature exhaustion of B cells may contribute to poor antibody responses against HIV in infected individuals.

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Pre-vaccination and early B cell signatures predict antibody response to SARS-CoV-2 mRNA vaccine

10.1101/2021.07.06.21259528 ◽

2021 ◽

Author(s):

Lela Kardava ◽

Nicholas Rachmaninoff ◽

William Lau ◽

Clarisa Buckner ◽

Krittin Trihemasava ◽

...

Keyword(s):

Antibody Response ◽

B Cell ◽

Response Variability ◽

Antibody Responses ◽

Igg Antibody ◽

Memory B Cell ◽

Post Vaccination ◽

Highly Effective ◽

Antibody Levels ◽

Early Indicators

SARS-CoV-2 mRNA vaccines are highly effective, although weak antibody responses are seen in some individuals with correlates of immunity that remain poorly understood. Here we longitudinally dissected antibody, plasmablast, and memory B cell (MBC) responses to the two-dose Moderna mRNA vaccine in SARS-CoV-2-uninfected adults. Robust, coordinated IgA and IgG antibody responses were preceded by bursts of spike-specific plasmablasts after both doses, but earlier and more intensely after dose two. Distinct antigen-specific MBC populations also emerged post-vaccination with varying kinetics. We identified antigen non-specific pre-vaccination MBC and post-vaccination plasmablasts after dose one and their spike-specific counterparts early after dose two that correlated with subsequent antibody levels. These baseline and response signatures can thus provide early indicators of serological efficacy and explain response variability in the population.

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Airway antibodies wane rapidly after COVID-19 but B cell memory is generated across disease severity

10.1101/2020.11.25.20238592 ◽

2020 ◽

Author(s):

Alberto Cagigi ◽

Meng Yu ◽

Sara Falck-Jones ◽

Sindhu Vangeti ◽

Björn Österberg ◽

...

Keyword(s):

B Cells ◽

Immune Responses ◽

B Cell ◽

Disease Severity ◽

Severe Disease ◽

Memory B Cells ◽

Antibody Responses ◽

Full Spectrum ◽

Viral Spread ◽

Specific Memory

AbstractUnderstanding immune responses following SARS-CoV-2 infection in relation to COVID-19 severity is critical for predicting the effects of long-term immunological memory on viral spread. Here we longitudinally assessed systemic and airway immune responses against SARS-CoV-2 in a well-characterized cohort of 147 infected individuals representing the full spectrum of COVID-19 severity; from asymptomatic infection to fatal disease. High systemic and airway antibody responses were elicited in patients with moderate to severe disease, and while systemic IgG levels were maintained after acute disease, airway IgG and IgA declined significantly. In contrast, individuals with mild symptoms showed significantly lower antibody responses but their levels of antigen-specific memory B cells were comparable with those observed in patients with moderate to severe disease. This suggests that antibodies in the airways may not be maintained at levels that prevent local virus entry upon re-exposure and therefore protection via activation of the memory B cell pool is critical.SummaryCOVID-19 severity determines the level of systemic and airway IgG and IgA but while IgG are maintained in plasma during convalescence, antibodies wane rapidly in the airways.However, comparable levels of antigen-specific memory B cells are generated across disease severity.

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Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

PLoS ONE ◽

10.1371/journal.pone.0244855 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0244855

Author(s):

Krista L. Newell ◽

Deanna C. Clemmer ◽

Justin B. Cox ◽

Yetunde I. Kayode ◽

Victoria Zoccoli-Rodriguez ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Peripheral Blood ◽

Respiratory Illness ◽

Significant Negative Correlation ◽

Memory B Cells ◽

Antibody Responses ◽

Symptom Duration ◽

Memory B Cell ◽

Duration Of Symptoms

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity.

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