The Influence of Immune Complex-Bearing Follicular Dendritic Cells on the IgM Response, Ig Class Switching, and Production of High Affinity IgG
| Autor: | John G. Tew, Andras K. Szakal, Yiiksel Aydar, Selvakumar Sukumar |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Time Factors
Immunology Cell Antigen-Antibody Complex Cell Communication Biology Ligands Lymphocyte Activation Affinity maturation Mice Low affinity Immune system Cytidine Deaminase medicine Animals Immunology and Allergy Cells Cultured B-Lymphocytes Follicular dendritic cells Nitrohydroxyiodophenylacetate Cytidine deaminase Immunoglobulin Class Switching Molecular biology Coculture Techniques Immune complex Mice Inbred C57BL medicine.anatomical_structure Immunoglobulin M Immunoglobulin class switching Immunoglobulin G Receptors Complement 3d Binding Sites Antibody Dendritic Cells Follicular |
| Zdroj: | The Journal of Immunology. 174:5358-5366 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.174.9.5358 |
| Popis: | It is believed that Ag in immune complexes (ICs) on follicular dendritic cells (FDCs) selects high affinity B cells and promotes affinity maturation. However, selection has been documented in the absence of readily detectable ICs on FDCs, suggesting that FDC-ICs may not be important. These results prompted experiments to test the hypothesis that IC-bearing murine FDCs can promote high affinity IgG responses by selecting B cells after stimulating naive IgM+ cells to mature and class switch. Coculturing naive λ+ B cells, FDCs, (4-hydroxy-3-nitrophenyl)acetyl-chicken γ-globulin (CGG) + anti-CGG ICs, and CGG-primed T cells resulted in FDC-lymphocyte clusters and production of anti-4-hydroxy-5-iodo-3-nitrophenyl acetyl. Class switching was indicated by a shift from IgM to IgG, and affinity maturation was indicated by a change from mostly low affinity IgM and IgG in the first week to virtually all high affinity IgG anti-4-hydroxy-5-iodo-3-nitrophenyl acetyl in the second week. Class switching and affinity maturation were easily detectable in the presence of FDCs bearing appropriate ICs, but not in the absence of FDCs. Free Ag plus FDCs resulted in low affinity IgG, but affinity maturation was only apparent when FDCs bore ICs. Class switching is activation-induced cytidine deaminase (AID) dependent, and blocking FDC-CD21 ligand-B cell CD21 interactions inhibited FDC-IC-mediated enhancement of AID production and the IgG response. In short, these data support the concept that ICs on FDCs can promote AID production, class switching, and maturation of naive IgM+ B cells, and further suggest that the IC-bearing FDCs help select high affinity B cells that produce high affinity IgG. |
| Databáze: | OpenAIRE |
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