Ligation of CD27 on B Cells In Vivo during Primary Immunization Enhances Commitment to Memory B Cell Responses

• Published in: The Journal of immunology (1950) 2003-12, Vol.171 (11), p.5876-5881
• Main Authors: Raman, Vanitha S, Akondy, Rama S, Rath, Satyajit, Bal, Vineeta, George, Anna
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - transplantation; CD40 Antigens - immunology; CD40 Antigens - physiology; Epitopes, B-Lymphocyte - metabolism; gamma-Globulins - administration & dosage; gamma-Globulins - immunology; Immune Sera - metabolism; Immunization, Secondary; Immunologic Memory; Lymphocyte Activation - immunology; Lymphocyte Count; Mice; Mice, Inbred BALB C; Nitrophenols - administration & dosage; Nitrophenols - immunology; Phenylacetates; Plasma Cells - immunology; Plasma Cells - metabolism; Protein Binding - immunology; Signal Transduction - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 7 - metabolism; Tumor Necrosis Factor Receptor Superfamily, Member 7 - physiology; Up-Regulation - immunology; Vaccination
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.11.5876

Ligation of CD27 on B cells has been shown to inhibit terminal differentiation of activated murine B cells into plasma cells. We show in this study that this inhibition is accompanied by an enhanced movement of activated B cells toward differentiation into memory cells. Treatment of mice with anti-CD27 during immunization leads to the generation of greater numbers of Ag-binding B cells in draining lymph nodes that persist for longer periods of time, and they contain a greater proportion of cells of a postgerminal center phenotype. Limiting dilution analyses reveal that they contain a higher frequency of cells that can be stimulated to secrete specific IgG, and adoptive transfer experiments confirm that they can generate higher secondary responses in carrier-primed recipients. Remarkably, significant secondary responses are also seen following primary immunization with a T-independent Ag in the presence of anti-CD27, confirming that ligation of CD27 on B cells during priming induces differentiation into the memory lineage. Treatment with anti-CD27 during priming also increases the average affinity of the secondary response, suggesting that high affinity clones generated early in a primary response may normally differentiate preferentially into plasma cells and are rescued from this fate by CD27 ligation. Anti-CD40 treatment shows similar effects in vivo. However, unlike CD27, CD40 coligation also enhances proliferation, survival, and isotype switching of LPS-stimulated B cells, suggesting that the two receptors may enhance commitment to B cell memory by different mechanisms, or that a common mechanism is used through both receptors that does not involve cell cycle control or survival.