Spatially regulated protease activity in lymph nodes renders B cell follicles a sanctuary for retention of intact antigens
Aung, A.; Cui, A.; Soleimany, A. P.; Bukenya, M.; Lee, H.; Cottrell, C. A.; Silva, M.; Kirkpatrick, J. D.; Amlashi, P.; Remba, T. K.; Xiao, S.; Froehle, L. M.; Abraham, W.; Adams, J.; Suh, H.; Huyett, P.; Kwon, D. S.; Hacohen, N.; Schief, W. R.; Bhatia, S. N.; Irvine, D. J.; Gregory, J. R.
Show abstract
The structural integrity of vaccine antigens is critical, as antigen degradation in vivo could eliminate neutralizing epitopes and create competing B cell responses against irrelevant breakdown products. Using FRET imaging and imaging zymography, we found that protease activity and antigen breakdown are spatially heterogeneous in lymph nodes. Following protein immunization, antigens are rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions of the tissue. By contrast, the follicles and follicular dendritic cell (FDC) networks exhibit low protease activity and antigen degradation rates. Immunization regimens targeting antigen rapidly to FDCs led to germinal centers (GCs) where responses to intact antigen were highly dominant, while traditional bolus immunizations led to weaker GC responses where more GC B cells bound to breakdown products than intact antigen. Thus, spatially-compartmentalized antigen proteolysis impacts humoral immunity and can be exploited to enhance vaccine-induced production of antibody responses against key pathogen structural epitopes.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Galectin-9 regulates the threshold of B cell activation and autoimmunity 95%
- Microtubules restrict F-actin to the immune synapse via GEF-H1 to maintain polarity in lymphocytes 95%
- Bronchus-associated macrophages are positioned for soluble antigen capture from the airway lumen and are capable of local Th2 cell activation 94%
Similar papers in this journal
Similar papers in this journal
- Pre-existing immunity modulates responses to mRNA boosters 96%
- BNT162b2 induced neutralizing and non-neutralizing antibody functions against SARSCoV-2 diminish with age 95%
- COVID-19 vaccination recruits and matures cross-reactive antibodies to conserved epitopes in endemic coronavirus Spike proteins 95%
Similar papers in this journal
- Potent Human Broadly SARS-CoV-2 Neutralizing IgA and IgG Antibodies Effective Against Omicron BA.1 and BA.2 95%
- Repertoire, function, and structure of serological antibodies induced by the R21/Matrix-M malaria vaccine 95%
- SARS-CoV-2 Spike protein suppresses CTL-mediated killing by inhibiting immune synapse assembly 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.