Germinal Center Hypoxia Potentiates Immunoglobulin Class Switch Recombination.

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,

SUBMITTER: Abbott RK 

PROVIDER: S-EPMC5123804 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature