Distinct Antibody Fc-profiles in Lymph During Homeostasis and Chronic HIV Infection

Antibodies play a critical role in the control of pathogens and tumors through their ability to recognize non-self and then direct immune-mediated destruction. Antibodies are generated by plasma cells or plasmablasts, located throughout the tissues, and are transported between blood, lymph, mucosal secretions, and tissues to survey all sites for pathogens or malignant cells. However, mounting evidence suggests antibodies that transit across compartments (from the blood to the brain, mucosal tissues, or placenta) differ from those in systemic circulation. Whether antibodies also differ as they transit from the blood into non-privileged tissues remains unclear. Thus, here we aimed to define the landscape of antibodies that exist within the blood and tissues and begin to define the properties that lead to antibody transfer across compartments.

To analyze tissue antibodies, we performed antibody profiling in chyle, a fluid component of lymph collected via the thoracic duct, contrasting these profiles to matched plasma samples.

Equivalent levels of pathogen-specific IgG antibodies and functions were observed across the plasma and lymph in people without HIV. However, this balance in IgG transfer was disrupted in people living with HIV, with significantly lower transfer ratios across several pathogen-specific IgG subpopulations in chyle.

Differential transfer of IgG was Fc-receptor dependent, pointing to a mechanism of transfer into tissues during inflammatory disease that may have a critical role in selecting the antibodies able to access the peripheral and lymphoid tissues.