| Title: |
Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination |
| Authors: |
Abbott, Robert K; Thayer, Molly; Labuda, Jasmine; Silva, Murillo; Philbrook, Phaethon; Cain, Derek W; Kojima, Hidefumi; Hatfield, Stephen; Sethumadhavan, Shalini; Ohta, Akio; Reinherz, Ellis L; Kelsoe, Garnett; Sitkovsky, Michail |
| Source: |
The Journal of Immunology ; volume 197, issue 10, page 4014-4020 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2016 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.1601401 |
| Availability: |
https://doi.org/10.4049/jimmunol.1601401; https://academic.oup.com/jimmunol/article-pdf/197/10/4014/61569708/1601401.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.5A9ECEB4 |
| Database: |
BASE |