The Physiological Landscape and Specificity of Antibody Repertoires
| Autor: | Lucia Csepregi, Kenneth B. Hoehn, Bruno E. Correia, Simon Friedensohn, Sai T. Reddy, Cédric R. Weber, Arkadij Kummer, Fabian Sesterhenn, Joseph M. Taft, Daniel Neumeier |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
biology Repertoire Spleen Germline 3. Good health 03 medical and health sciences 0302 clinical medicine Lymphatic system medicine.anatomical_structure Antibody Repertoire Antigen 030220 oncology & carcinogenesis Humoral immunity Immunology biology.protein medicine Antibody 030304 developmental biology |
| Popis: | Diverse antibody repertoires spanning multiple lymphoid organs (e.g., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity. Changes in their composition across lymphoid organs are a consequence of B-cell selection and migration events leading to a highly dynamic and unique physiological landscape of antibody repertoires upon antigenic challenge (e.g., vaccination). However, to what extent B cells encoding identical or similar antibody sequences (clones) are distributed across multiple lymphoid organs and how this is shaped by the strength of a humoral response, remains largely unexplored. Here, we performed an in-depth systems analysis of antibody repertoires across multiple distinct lymphoid organs of immunized mice, and discovered that organ-specific antibody repertoire features (e.g., germline V-gene usage and clonal expansion profiles) equilibrated upon a strong humoral response (multiple immunizations and high serum titers). This resulted in a surprisingly high degree of repertoire consolidation, characterized by highly connected and overlapping B-cell clones across multiple lymphoid organs. Finally, we revealed distinct physiological axes indicating clonal migrations and showed that antibody repertoire consolidation directly correlated with antigen-specificity. Our study uncovered how a strong humoral response resulted in a more uniform but redundant physiological landscape of antibody repertoires, indicating that increases in antibody serum titers were a result of synergistic contributions from antigen-specific B-cell clones distributed across multiple lymphoid organs. Our findings provide valuable insights for the assessment and design of vaccine strategies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|