April 25, 2019

Low oxygen and antibody responses

Mark Boothby and colleagues are exploring the factors that contribute to antibody production and quality, which are key to our defense against pathogens and response to vaccines.

Antibody production by B cells (humoral immunity) is a key part of our defense system against pathogens. Helper T cells interact with B cells in germinal centers — lymph tissue microstructures — to enhance antibody production and quality.

Hypoxia (low oxygen) is a normal feature of germinal centers, and Sung Hoon Cho, PhD, Mark Boothby, MD, PhD, and colleagues have now investigated how hypoxia impacts T cell help.

They showed that a pair of proteins that respond to low oxygen, hypoxia-inducible factors (HIFs), are vital to T cell help during humoral immune responses. They report in the Proceedings of the National Academy of Sciences that HIFs promote antibody production by shifting the balance between different types of helper T cells and regulating T cell metabolism and cytokine production.

The findings are important for vaccine development and may have broader implications for understanding T helper cell cytokine production in pathophysiological states where hypoxia is common, such as atherosclerosis, rheumatoid arthritis, viral infection and cancer.

This research was supported by grants from the National Institutes of Health (AI113292, HL106812, OD018015, CA068485, DK020593, DK101791, DK081646).