https://orcid.org/0000-0002-2957-9680
-
Views
-
Cite
Cite
Robert K Abbott, Molly Thayer, Jasmine Labuda, Murillo Silva, Phaethon Philbrook, Derek W Cain, Hidefumi Kojima, Stephen Hatfield, Shalini Sethumadhavan, Akio Ohta, Ellis L Reinherz, Garnett Kelsoe, Michail Sitkovsky, Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination, The Journal of Immunology, Volume 197, Issue 10, November 2016, Pages 4014–4020, https://doi.org/10.4049/jimmunol.1601401
Close - Share Icon Share
Abstract
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.
