Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin

Andrews, Sarah F.; Chambers, Michael; Schramm, Chaim A.; Plyler, Jason; Raab, Julie E.; Kanekiyo, Masaru; Gillespie, Rebecca A.; Ransier, Amy; Darko, Sam; Hu, Jianfei; Chen, Xuejun; Yassine, Hadi M.; Boyington, Jeffrey C.; Crank, Michelle C.; Chen, Grace L.; Coates, Emily E.; Mascola, John R.; Douek, Daniel C.; Graham, Barney S.; Ledgerwood, Julie E.; McDermott, Adrian B.

doi:10.1016/j.immuni.2019.06.024

Cited by 115 publications

(157 citation statements)

References 75 publications

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“…As a comparator non-malaria antigen, we used influenza surface glycoprotein hemagglutinin (HA)-the principal target of influenza-specific neutralizing antibodies. Using the Meso Scale Discovery (MSD) assay, which is an electrochemiluminescent-based ELISA replacement assay (22), we found in the Mali cohort a high prevalence of serum IgG reactivity specific for the influenza A subtypes H1N1 or H3N2, which have been reported to circulate in Mali (23) ( Fig. S1).…”

Section: Confirmation Of Specificity Of Pfama1/pfmsp1 and Ha B Cell Pmentioning

confidence: 99%

“…To more directly confirm the antigen specificity of the B cell probes, we sorted single probe-positive B cells from adult Malian PBMC samples (gating strategy in Fig. 1 A-D) and amplified the BCR using reverse transcription and PCR followed by Sanger sequencing (22,28). Heavy chain and corresponding light chain sequences of four Pf-and HA-probe binding B cells were chosen for cloning and expression as recombinant human monoclonal antibodies (hmAb).…”

Section: Confirmation Of Specificity Of Pfama1/pfmsp1 and Ha B Cell Pmentioning

confidence: 99%

“…cDNA was directly made from sorted cells using Superscript III Reverse Transcriptase (ThermoFisher) and random hexamers. Immunoglobulin heavy and light chain (kappa and lambda) genes were then PCR amplified separately with two rounds of nested PCR with 50 cycles each, using DreamTaq Mastermix (ThermoFisher), as described previously with some modifications (22,28). PCR products were Sanger sequenced by Genscript and sequences were analyzed using IMGT/V-QUEST (33).…”

Section: Single-cell Bcr Amplification Sequence Analysis and Recombimentioning

confidence: 99%

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Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM

Hopp

Diouf

Miura

et al. 2020

Preprint

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IgG antibodies are known to play a central role in naturally acquired immunity to blood-stage malaria in humans, but little is known about the IgM response to blood-stage malaria, the mechanisms by which IgM may protect, or the underlying biology of Plasmodium falciparum (Pf)-specific IgM B cells. In a Mali cohort spanning infants to adults we conducted a longitudinal analysis of B cells specific for the Pf blood-stage antigens AMA1 and MSP1, as well as the comparator antigen influenza hemagglutinin (HA). At the uninfected baseline, before the malaria season, Pf-specific memory B cells (MBCs) in children are disproportionally IgM + and only gradually shift to IgG + with age, in contrast to HA-specific MBCs that are predominantly IgG + from infancy to adulthood. In response to acute febrile malaria, Pf-specific IgM B cells increase in frequency and upregulate activation and co-stimulatory markers. B cell receptor (BCR) analysis showed that Pf-specific IgM B cells are somatically hypermutated at levels comparable to HA-specific IgG B cells. Finally, IgM antibodies from the plasma of malaria-exposed individuals were comparable to IgG in inhibiting Pf blood-stage growth in vitro, and significantly better at enhancing phagocytosis of Pf merozoites, suggesting that IgM may protect through both direct neutralization and opsonization. Thus, somatically hypermutated Pf-specific IgM MBCs dominate in early life, are activated and expand during acute malaria and are associated with plasma IgM that inhibits parasite growth in vitro.

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Section: Confirmation Of Specificity Of Pfama1/pfmsp1 and Ha B Cell Pmentioning

confidence: 99%

Section: Confirmation Of Specificity Of Pfama1/pfmsp1 and Ha B Cell Pmentioning

confidence: 99%

Section: Single-cell Bcr Amplification Sequence Analysis and Recombimentioning

confidence: 99%

See 1 more Smart Citation

Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM

Hopp

Diouf

Miura

et al. 2020

Preprint

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“…In humans, both switched immunoglobulin (swIg + ) and immunoglobulin M (IgM + ) memory cells have been described, as well as "atypical" MBCs that express FCRL4 or FCRL5 and/or lack expression of the canonical MBC surface marker CD27 (2,3). Various activated B cell subsets, which appear transiently after infection or vaccination, have also been reported (4)(5)(6). In mice, MBCs can be subcategorized based on their expression of Ig isotype as well as other surface markers, such as CD80, PD-L2, and CD73 (2,7).…”

mentioning

confidence: 99%

Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine

Wec

Haslwanter

Abdiche

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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A comprehensive understanding of the development and evolution of human B cell responses induced by pathogen exposure will facilitate the design of next-generation vaccines. Here, we utilized a high-throughput single B cell cloning technology to longitudinally track the human B cell response to the yellow fever virus 17D (YFV-17D) vaccine. The early memory B cell (MBC) response was mediated by both classical immunoglobulin M (IgM) (IgM+CD27+) and switched immunoglobulin (swIg+) MBC populations; however, classical IgM MBCs waned rapidly, whereas swIg+and atypical IgM+and IgD+MBCs were stable over time. Affinity maturation continued for 6 to 9 mo following vaccination, providing evidence for the persistence of germinal center activity long after the period of active viral replication in peripheral blood. Finally, a substantial fraction of the neutralizing antibody response was mediated by public clones that recognize a fusion loop-proximal antigenic site within domain II of the viral envelope glycoprotein. Overall, our findings provide a framework for understanding the dynamics and complexity of human B cell responses elicited by infection and vaccination.

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“…Circulating MBCs adapted to the H3 head domain were detected within ∼4 wk of symptom onset. Evidence that HA-reactive MBCs with increased levels of somatic hypermutation are formed many months after HA vaccination in humans indicates that affinity maturation of MBCs continues long after any early switch by GCs to predominantly plasma cell production (Andrews et al 2019;Matsuda et al 2019).…”

Section: B-cell Response 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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Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin

Cited by 115 publications

References 75 publications

Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM

Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM

Longitudinal dynamics of the human B cell response to the yellow fever 17D vaccine

Immunity to Influenza Infection in Humans

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