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Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.

Publication ,  Journal Article
Abbott, RK; Thayer, M; Labuda, J; Silva, M; Philbrook, P; Cain, DW; Kojima, H; Hatfield, S; Sethumadhavan, S; Ohta, A; Reinherz, EL; Kelsoe, G ...
Published in: J Immunol
November 15, 2016

Germinal centers (GCs) are anatomic sites where B cells undergo secondary diversification to produce high-affinity, class-switched Abs. We hypothesized that proliferating B cells in GCs create a hypoxic microenvironment that governs their further differentiation. Using molecular markers, we found GCs to be predominantly hypoxic. Compared to normoxia (21% O2), hypoxic culture conditions (1% O2) in vitro accelerated class switching and plasma cell formation and enhanced expression of GL-7 on B and CD4+ T cells. Reversal of GC hypoxia in vivo by breathing 60% O2 during immunization resulted in reduced frequencies of GC B cells, T follicular helper cells, and plasmacytes, as well as lower expression of ICOS on T follicular helper cells. Importantly, this reversal of GC hypoxia decreased Ag-specific serum IgG1 and reduced the frequency of IgG1+ B cells within the Ag-specific GC. Taken together, these observations reveal a critical role for hypoxia in GC B cell differentiation.

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2016

Volume

197

Issue

10

Start / End Page

4014 / 4020

Location

United States

Related Subject Headings

  • Recombination, Genetic
  • Plasma Cells
  • Oxygen
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Immunoglobulins
  • Immunoglobulin G
  • Immunoglobulin Class Switching
 

Citation

APA
Chicago
ICMJE
MLA
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Abbott, R. K., Thayer, M., Labuda, J., Silva, M., Philbrook, P., Cain, D. W., … Sitkovsky, M. (2016). Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination. J Immunol, 197(10), 4014–4020. https://doi.org/10.4049/jimmunol.1601401
Abbott, Robert K., Molly Thayer, Jasmine Labuda, Murillo Silva, Phaethon Philbrook, Derek W. Cain, Hidefumi Kojima, et al. “Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.J Immunol 197, no. 10 (November 15, 2016): 4014–20. https://doi.org/10.4049/jimmunol.1601401.
Abbott RK, Thayer M, Labuda J, Silva M, Philbrook P, Cain DW, et al. Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination. J Immunol. 2016 Nov 15;197(10):4014–20.
Abbott, Robert K., et al. “Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.J Immunol, vol. 197, no. 10, Nov. 2016, pp. 4014–20. Pubmed, doi:10.4049/jimmunol.1601401.
Abbott RK, Thayer M, Labuda J, Silva M, Philbrook P, Cain DW, Kojima H, Hatfield S, Sethumadhavan S, Ohta A, Reinherz EL, Kelsoe G, Sitkovsky M. Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination. J Immunol. 2016 Nov 15;197(10):4014–4020.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

November 15, 2016

Volume

197

Issue

10

Start / End Page

4014 / 4020

Location

United States

Related Subject Headings

  • Recombination, Genetic
  • Plasma Cells
  • Oxygen
  • Mice, Inbred C57BL
  • Mice
  • Lymphocyte Activation
  • Immunology
  • Immunoglobulins
  • Immunoglobulin G
  • Immunoglobulin Class Switching