αv Integrins regulate germinal center B cell responses through noncanonical autophagy

The Journal of Clinical Investigation
Fiona RasoMridu Acharya

Abstract

Germinal centers (GCs) are major sites of clonal B cell expansion and generation of long-lived, high-affinity antibody responses to pathogens. Signaling through TLRs on B cells promotes many aspects of GC B cell responses, including affinity maturation, class switching, and differentiation into long-lived memory and plasma cells. A major challenge for effective vaccination is identifying strategies to specifically promote GC B cell responses. Here, we have identified a mechanism of regulation of GC B cell TLR signaling, mediated by αv integrins and noncanonical autophagy. Using B cell-specific αv-KO mice, we show that loss of αv-mediated TLR regulation increased GC B cell expansion, somatic hypermutation, class switching, and generation of long-lived plasma cells after immunization with virus-like particles (VLPs) or antigens associated with TLR ligand adjuvants. Furthermore, targeting αv-mediated regulation increased the magnitude and breadth of antibody responses to influenza virus vaccination. These data therefore identify a mechanism of regulation of GC B cells that can be targeted to enhance antibody responses to vaccination.

References

Apr 12, 2002·Nature·Elizabeth A LeadbetterAnn Marshak-Rothstein
Sep 5, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mark LucasAdam Lacy-Hulbert
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea JegerlehnerMartin F Bachmann
Mar 16, 2007·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A Lacy-HulbertR Abdi
Feb 26, 2008·Nature Immunology·Jonathan C KaganRuslan Medzhitov
Jun 27, 2009·Nature Reviews. Immunology·Gregory M Barton, Jonathan C Kagan
Sep 1, 2009·Journal of Immunological Methods·Thomas TillerHedda Wardemann
Nov 17, 2009·Journal of Cell Science·Adam ByronMartin J Humphries
Dec 24, 2009·Nature Reviews. Cancer·Jay S Desgrosellier, David A Cheresh
Sep 18, 2010·Science·Miwa SasaiAkiko Iwasaki
Dec 20, 2011·Molecular Immunology·Zhiping ZhangHugh Salter
Jan 10, 2012·Annual Review of Immunology·Gabriel D Victora, Michel C Nussenzweig
Apr 17, 2012·Immunological Reviews·Anthony L DeFrancoBaidong Hou
Oct 10, 2012·Proceedings of the National Academy of Sciences of the United States of America·Christopher H CleggSteven G Reed
Nov 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Tatiana GianniGabriella Campadelli-Fiume
Jan 29, 2013·Nature Immunology·Niccolò PengoSimone Cenci
Jun 14, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jonathan M Clingan, Mehrdad Matloubian
Aug 13, 2013·Nature Immunology·Michael G OverstreetDeborah J Fowell
Dec 7, 2013·Nature Medicine·Steven G ReedChristopher B Fox
Apr 9, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shaun W JacksonDavid J Rawlings
Apr 18, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiaoming WangJason G Cyster
Jul 24, 2014·Proceedings of the National Academy of Sciences of the United States of America·Derek C Rookhuizen, Anthony L DeFranco
Aug 31, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc A SchwartzDavid J Rawlings
Mar 12, 2016·Nature Communications·Mridu AcharyaAdam Lacy-Hulbert
Jun 16, 2016·F1000Research·Anthony L DeFranco
Jan 16, 2017·Current Opinion in Immunology·Oliver Bannard, Jason G Cyster
Feb 12, 2017·Science·Nuria Martinez-MartinFacundo D Batista

❮ Previous
Next ❯

Citations

Aug 30, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mridu AcharyaAdam Lacy-Hulbert
Dec 12, 2018·Nature Reviews. Immunology·Alexander J Clarke, Anna Katharina Simon
Feb 23, 2019·Journal of Cell Science·Bradlee L Heckmann, Douglas R Green
Aug 21, 2018·The Journal of Clinical Investigation·Jeremy S Leventhal
Oct 7, 2020·Trends in Biochemical Sciences·Martijn A NolteCoert Margadant
Nov 25, 2021·Current Rheumatology Reports·Anne B Satterthwaite
Jan 19, 2022·Immunological Reviews·Mridu Acharya, Shaun W Jackson

❮ Previous
Next ❯

Methods Mentioned

BETA
lipidation
FACS
ELISA
flow cytometry
scintillation
electrophoresis
PCR

Software Mentioned

Volocity
GraphPad Prism
FlowJo

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.