The Multifaceted B Cell Response to Influenza Virus

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2019 Jan 9

PMID 30617116

Citations 67

Authors

Jonathan H Lam

Nicole Baumgarth

Affiliations

Soon will be listed here.

Abstract

Protection from yearly recurring, highly acute infections with a pathogen that rapidly and continuously evades previously induced protective neutralizing Abs, as seen during seasonal influenza virus infections, can be expected to require a B cell response that is too highly variable, able to adapt rapidly, and able to reduce morbidity and death when sterile immunity cannot be garnered quickly enough. As we outline in this , the influenza-specific B cell response is exactly that: it is multifaceted, involves both innate-like and conventional B cells, provides early and later immune protection, employs B cells with distinct BCR repertoires and distinct modes of activation, and continuously adapts to the ever-changing virus while enhancing overall protection. A formidable response to a formidable pathogen.

Citing Articles

Memory Cells in Infection and Autoimmunity: Mechanisms, Functions, and Therapeutic Implications.

Giri S, Batra L Vaccines (Basel). 2025; 13(2).

PMID: 40006751 PMC: 11860616. DOI: 10.3390/vaccines13020205.

Structural mapping of polyclonal IgG responses to HA after influenza virus vaccination or infection.

Leon A, Rodriguez A, Richey S, Torrents de la Pena A, Wolters R, Jackson A mBio. 2025; 16(3):e0203024.

PMID: 39912630 PMC: 11898601. DOI: 10.1128/mbio.02030-24.

The survival of B cells is compromised in kidney disease.

Peroumal D, Jawale C, Choi W, Rahimi H, Antos D, Li D Nat Commun. 2024; 15(1):10842.

PMID: 39738044 PMC: 11685736. DOI: 10.1038/s41467-024-55187-w.

An Integrated Signaling Threshold Initiates IgG Response toward Virus-like Immunogens.

Wholey W, Meyer A, Yoda S, Mueller J, Mathenge R, Chackerian B J Immunol. 2024; 213(8):1061-1075.

PMID: 39212443 PMC: 11458362. DOI: 10.4049/jimmunol.2400101.

Immunological characterization and comparison of children with COVID-19 from their adult counterparts at single-cell resolution.

Jia R, Li Z, Hu S, Chang H, Zeng M, Liu P Front Immunol. 2024; 15:1358725.

PMID: 39148728 PMC: 11325098. DOI: 10.3389/fimmu.2024.1358725.

References

Lee F, Halliley J, Walsh E, Moscatiello A, Kmush B, Falsey A . Circulating human antibody-secreting cells during vaccinations and respiratory viral infections are characterized by high specificity and lack of bystander effect. J Immunol. 2011; 186(9):5514-21. PMC: 3726212. DOI: 10.4049/jimmunol.1002932. View

Wang H, Coligan J, Morse 3rd H . Emerging Functions of Natural IgM and Its Fc Receptor FCMR in Immune Homeostasis. Front Immunol. 2016; 7:99. PMC: 4791374. DOI: 10.3389/fimmu.2016.00099. View

MacLennan I, Toellner K, Cunningham A, Serre K, Sze D, Zuniga E . Extrafollicular antibody responses. Immunol Rev. 2003; 194:8-18. DOI: 10.1034/j.1600-065x.2003.00058.x. View

Sealy R, Surman S, Hurwitz J, Coleclough C . Antibody response to influenza infection of mice: different patterns for glycoprotein and nucleocapsid antigens. Immunology. 2003; 108(4):431-9. PMC: 1782924. DOI: 10.1046/j.1365-2567.2003.01615.x. View

McCarthy K, Watanabe A, Kuraoka M, Do K, McGee C, Sempowski G . Memory B Cells that Cross-React with Group 1 and Group 2 Influenza A Viruses Are Abundant in Adult Human Repertoires. Immunity. 2018; 48(1):174-184.e9. PMC: 5810956. DOI: 10.1016/j.immuni.2017.12.009. View

Schmitz N, Kurrer M, Bachmann M, Kopf M . Interleukin-1 is responsible for acute lung immunopathology but increases survival of respiratory influenza virus infection. J Virol. 2005; 79(10):6441-8. PMC: 1091664. DOI: 10.1128/JVI.79.10.6441-6448.2005. View

Arimori Y, Nakamura R, Yamada H, Shibata K, Maeda N, Kase T . Type I interferon limits influenza virus-induced acute lung injury by regulation of excessive inflammation in mice. Antiviral Res. 2013; 99(3):230-7. DOI: 10.1016/j.antiviral.2013.05.007. View

Phan T, Paus D, Chan T, Turner M, Nutt S, Basten A . High affinity germinal center B cells are actively selected into the plasma cell compartment. J Exp Med. 2006; 203(11):2419-24. PMC: 2118125. DOI: 10.1084/jem.20061254. View

Shen P, Fillatreau S . Antibody-independent functions of B cells: a focus on cytokines. Nat Rev Immunol. 2015; 15(7):441-51. DOI: 10.1038/nri3857. View

10.

Junt T, Moseman E, Iannacone M, Massberg S, Lang P, Boes M . Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells. Nature. 2007; 450(7166):110-4. DOI: 10.1038/nature06287. View

11.

Kumar V, Scandella E, Danuser R, Onder L, Nitschke M, Fukui Y . Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway. Blood. 2010; 115(23):4725-33. DOI: 10.1182/blood-2009-10-250118. View

12.

Richards K, Topham D, Chaves F, Sant A . Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus. J Immunol. 2010; 185(9):4998-5002. DOI: 10.4049/jimmunol.1001395. View

13.

GeurtsvanKessel C, Willart M, Bergen I, van Rijt L, Muskens F, Elewaut D . Dendritic cells are crucial for maintenance of tertiary lymphoid structures in the lung of influenza virus-infected mice. J Exp Med. 2009; 206(11):2339-49. PMC: 2768850. DOI: 10.1084/jem.20090410. View

14.

Jacob J, Kelsoe G . In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J Exp Med. 1992; 176(3):679-87. PMC: 2119370. DOI: 10.1084/jem.176.3.679. View

15.

Batista F, Harwood N . The who, how and where of antigen presentation to B cells. Nat Rev Immunol. 2008; 9(1):15-27. DOI: 10.1038/nri2454. View

16.

Fu Y, Zhang Z, Sheehan J, Avnir Y, Ridenour C, Sachnik T . A broadly neutralizing anti-influenza antibody reveals ongoing capacity of haemagglutinin-specific memory B cells to evolve. Nat Commun. 2016; 7:12780. PMC: 5027281. DOI: 10.1038/ncomms12780. View

17.

ROOST H, Bachmann M, Haag A, Kalinke U, Pliska V, Hengartner H . Early high-affinity neutralizing anti-viral IgG responses without further overall improvements of affinity. Proc Natl Acad Sci U S A. 1995; 92(5):1257-61. PMC: 42498. DOI: 10.1073/pnas.92.5.1257. View

18.

Koutsakos M, Wheatley A, Loh L, Clemens E, Sant S, Nussing S . Circulating T cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity. Sci Transl Med. 2018; 10(428). DOI: 10.1126/scitranslmed.aan8405. View

19.

Gram A, Sun C, Landman S, Oosenbrug T, Koppejan H, Kwakkenbos M . Human B cells fail to secrete type I interferons upon cytoplasmic DNA exposure. Mol Immunol. 2017; 91:225-237. DOI: 10.1016/j.molimm.2017.08.025. View

20.

Vanderven H, Jegaskanda S, Wheatley A, Kent S . Antibody-dependent cellular cytotoxicity and influenza virus. Curr Opin Virol. 2017; 22:89-96. DOI: 10.1016/j.coviro.2016.12.002. View