The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19

Kaneko, Naoki; Kuo, Hsiao-Hsuan; Boucau, Julie; Farmer, Jocelyn R.; Allard-Chamard, Hugues; Mahajan, Vinay S.; Piechocka-Trocha, Alicja; Lefteri, Kristina; Osborn, Matthew; Bals, Julia; Bartsch, Yannic C.; Bonheur, Nathalie; Caradonna, Timothy M.; Chevalier, Josh; Chowdhury, Fatema Z.; Diefenbach, Thomas; Einkauf, Kevin; Fallon, Jon; Feldman, Jared; Finn, Kelsey; García-Broncano, Pilar; Hartana, Ciputra Adijaya; Hauser, Blake M.; Jiang, Chenyang; Kapłonek, Paulina; Karpell, Marshall; Koscher, Eric C.; Lian, Xiaodong; Liu, Huan; Liu, Jinqing; Ly, Ngoc L.; Michell, Ashlin; Rassadkina, Yelizaveta; Seiger, Kyra; Sessa, Libera; Shin, Sally; Singh, Nishant K.; Sun, Weiwei; Sun, Xiaoming; Ticheli, Hannah; Waring, Michael T.; Zhu, Alex; Li, Jonathan; Lingwood, Daniel; Schmidt, Aaron; Lichterfeld, Matthias; Walker, Bruce D.; Yu, Xu G.; Padera, Robert F.; Pillai, Shiv; Group, Massachusetts Consortium on Pathogen Readiness Specimen Working

doi:10.2139/ssrn.3652322

Cited by 35 publications

(42 citation statements)

References 36 publications

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“…Indeed, the extremely potent antibodies and the antibodies against the S2 subunit are unlikely to contribute to the overall neutralizing titers because they are too rare and too poor neutralizers respectively to be able to make the difference. The observed antibody repertoire of convalescent patients may be a consequence of the loss of Bcl-6-expressing follicular helper T cells and the loss of germinal centers in patients which may limit and constrain the B cell affinity maturation (Kaneko et al, 2020). It is therefore important to perform similar studies following vaccination as it is likely that the repertoire of neutralizing antibodies induced by vaccination may be different from the one described here.…”

Section: Discussionmentioning

confidence: 88%

Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

Andreano

Nicastri

Paciello

et al. 2020

Preprint

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SUMMARYHuman monoclonal antibodies are safe, preventive and therapeutic tools, that can be rapidly developed to help restore the massive health and economic disruption caused by the Covid-19 pandemic. By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. Up to 65,9% of monoclonals neutralized the wild type virus at a concentration of >500 ng/mL, 23,6% neutralized the virus in the range of 100 - 500 ng/mL and 9,1% had a neutralization potency in the range of 10 - 100 ng/mL. Only 1,4% neutralized the authentic virus with a potency of 1-10 ng/mL. We found that the most potent neutralizing antibodies are extremely rare and recognize the RBD, followed in potency by antibodies that recognize the S1 domain, the S-protein trimeric structure and the S2 subunit. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2.One Sentence SummaryExtremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions.

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Section: Discussionmentioning

confidence: 88%

Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

Andreano

Nicastri

Paciello

et al. 2020

Preprint

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“…Since air pollution exposure has been associated with increased SARS-CoV-2 infection and COVID-19-associated mortality, [56][57][58][59][60][61][62] reducing pollutant emissions and individual exposure may prevent pollutantinduced exacerbation of SARS-CoV-2 infection and COVID-19 disease. Because of the urgency of the current topic, we have also included nonpeerreviewed preprints as references, 58,60,70,119,123 so the legitimacy of these findings should be confirmed by peer-reviewed studies.…”

Section: Resultsmentioning

confidence: 99%

SARS‐CoV‐2 infection, COVID‐19 pathogenesis, and exposure to air pollution: What is the connection?

Woodby

Arnold

Valacchi

2020

Annals of the New York Academy of Sciences

126

113

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Exposure to air pollutants has been previously associated with respiratory viral infections, including influenza, measles, mumps, rhinovirus, and respiratory syncytial virus. Epidemiological studies have also suggested that air pollution exposure is associated with increased cases of SARS-CoV-2 infection and COVID-19-associated mortality, although the molecular mechanisms by which pollutant exposure affects viral infection and pathogenesis of COVID-19 remain unknown. In this review, we suggest potential molecular mechanisms that could account for this association. We have focused on the potential effect of exposure to nitrogen dioxide (NO 2), ozone (O 3), and particulate matter (PM) since there are studies investigating how exposure to these pollutants affects the life cycle of other viruses. We have concluded that pollutant exposure may affect different stages of the viral life cycle, including inhibition of mucociliary clearance, alteration of viral receptors and proteases required for entry, changes to antiviral interferon production and viral replication, changes in viral assembly mediated by autophagy, prevention of uptake by macrophages, and promotion of viral spread by increasing epithelial permeability. We believe that exposure to pollutants skews adaptive immune responses toward bacterial/allergic immune responses, as opposed to antiviral responses. Exposure to air pollutants could also predispose exposed populations toward developing COIVD-19associated immunopathology, enhancing virus-induced tissue inflammation and damage.

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“…Responses from T follicular helper (Tfh) cells are crucial to the development of robust humoral immunity through the formation of germinal centres and provision of co-stimulation (eg, CD40–CD40-L interactions) and cytokines (eg, IL-21) to B cells. 39 A post-mortem study of individuals who died of COVID-19 found an absence of germinal centres and an absence of BCL-6 + Tfh cells, 40 suggesting that inadequate activation of the Tfh response is one possible mechanism for the shortfall in durable antibody responses to SARS-CoV-2. However, a single-cell RNA sequencing study of the CD4 + T-cell response to SARS-CoV-2 found an increased proportion of Tfh cells in patients with severe disease compared with patients with mild disease.…”

Section: Cellular Immunity To Sars-cov-2mentioning

confidence: 99%

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

2020

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Understanding immune responses to severe acute respiratory syndrome coronavirus 2 is crucial to understanding disease pathogenesis and the usefulness of bridge therapies, such as hyperimmune globulin and convalescent human plasma, and to developing vaccines, antivirals, and monoclonal antibodies. A mere 11 months ago, the canvas we call COVID-19 was blank. Scientists around the world have worked collaboratively to fill in this blank canvas. In this Review, we discuss what is currently known about human humoral and cellular immune responses to severe acute respiratory syndrome coronavirus 2 and relate this knowledge to the COVID-19 vaccines currently in phase 3 clinical trials.

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The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19

Cited by 35 publications

References 36 publications

Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

Extremely potent human monoclonal antibodies from convalescent Covid-19 patients

SARS‐CoV‐2 infection, COVID‐19 pathogenesis, and exposure to air pollution: What is the connection?

SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates

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