Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.
Journal Article (Journal Article)
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.
- 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
- November 15, 2016
Volume / Issue
- 197 / 10
Start / End Page
- 4014 - 4020
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)
- United States