Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection

Sangster, Mark Y.; Nguyen-Contant, Phuong; Topham, David J.

doi:10.3390/pathogens8040167

Cited by 23 publications

(21 citation statements)

References 66 publications

(116 reference statements)

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“…Notably, three convalescent subjects in our analysis had undetectable RBD-reactive IgG levels but nevertheless had RBD-reactive IgG MBCs. This might reflect MBC production by germinal centers that remained active after recovery from infection (32). The proportion of subjects with MBCs reactive to the HCoVs OC43 and 229E was greater for the convalescent group than for the unexposed group, likely reflecting the increase in levels of S2-reactive MBCs in the convalescent group and cross-reactivity with HCoVs.…”

Section: Discussionmentioning

confidence: 96%

S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit

Nguyen-Contant

Embong

Kanagaiah

et al. 2020

mBio

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208

178

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The high susceptibility of humans to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the cause of coronavirus disease 2019 (COVID-19), reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and peripheral blood mononuclear cells (PBMCs) from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBC levels. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG, and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 were higher in convalescent subjects than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane. IMPORTANCE The recent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key issues are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and postinfection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study results also suggest that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

show abstract

Section: Discussionmentioning

confidence: 96%

S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit

Nguyen-Contant

Embong

Kanagaiah

et al. 2020

mBio

Self Cite

208

178

View full text Add to dashboard Cite

show abstract

“…Notably, three convalescent subjects in our analysis had undetectable RBD-reactive IgG, but nevertheless had RBD-reactive IgG MBCs. This might reflect MBC production by germinal centers that remained active after recovery from infection (29). The proportion of subjects with MBCs reactive to the HCoVs OC43 and 229E was greater for the convalescent group than the unexposed group, likely reflecting the increase in S2-reactive MBCs in the convalescent group and cross-reactivity with HCoVs.…”

Section: Discussionmentioning

confidence: 96%

S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit

Nguyen-Contant

Embong

Kanagaiah

et al. 2020

Preprint

Self Cite

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The high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane.IMPORTANCERecent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key questions are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and post-infection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study also suggests that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation.

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“…The B-cell response to IAV infection has recently been comprehensively reviewed (Krammer 2019) and is also discussed extensively in this volume by Wilson and colleagues (Wilson et al 2019). Here, we emphasize the role of MBCs in the B-cell response to seasonal IAV infection in influenza-immune adults (Sangster et al 2019). All proteins expressed by an infecting IAV can potentially activate B cells and generate specific antibodies (Abs) and MBCs, but the response is typically strongest against the more abundant structural proteins.…”

Section: B-cell Response To Seasonal Influenza Infectionmentioning

confidence: 99%

“…Until recently, fewer children were vaccinated, suggesting these early exposures are most likely to be from infections. The field has also recently realized that these early life exposures result in lifelong "imprinting" of the immune system, particularly in regard to antibody and memory B-cell specificities (for review, see Guthmiller and Wilson 2018;Lewnard and Cobey 2018;Francis et al 2019;Sangster et al 2019). The early infections also generate long-lived memory T cells, although whether a pattern of antigenic imprinting is created has not yet been shown.…”

Section: Cd8 + T-cell Responses To Seasonal Influenza Infectionmentioning

confidence: 99%

Immunity to Influenza Infection in Humans

Topham

DeDiego

Nogales

et al. 2019

Cold Spring Harb Perspect Med

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This review discusses the human immune responses to influenza infection with some insights from studies using animal models, such as experimental infection of mice. Recent technological advances in the study of human immune responses have greatly added to our knowledge of the infection and immune responses, and therefore much of the focus is on recent studies that have moved the field forward. We consider the complexity of the adaptive response generated by many sequential encounters through infection and vaccination.

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Role of Memory B Cells in Hemagglutinin-Specific Antibody Production Following Human Influenza A Virus Infection

Cited by 23 publications

References 66 publications

S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit

S Protein-Reactive IgG and Memory B Cell Production after Human SARS-CoV-2 Infection Includes Broad Reactivity to the S2 Subunit

S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit

Immunity to Influenza Infection in Humans

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