title: Ligation of CD27 on B cells in vivo during primary immunization enhances commitment to memory B cell responses.
abstract: 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.
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Vanitha S
authors.initials: VS
authors.lastname: Raman
authors.forename: Rama S
authors.initials: RS
authors.lastname: Akondy
authors.forename: Satyajit
authors.initials: S
authors.lastname: Rath
authors.forename: Vineeta
authors.initials: V
authors.lastname: Bal
authors.forename: Anna
authors.initials: A
authors.lastname: George
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000637:transplantation; D019013:CD40 Antigens / Q000276:immunology / Q000502:physiology; D018985:Epitopes, B-Lymphocyte / Q000378:metabolism; D007106:Immune Sera / Q000378:metabolism; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009596:Nitrophenols / Q000008:administration & dosage / Q000276:immunology; D010648:Phenylacetates; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology* / Q000378:metabolism* / Q000502:physiology; D015854:Up-Regulation / Q000276:immunology*; D014611:Vaccination; D005719:gamma-Globulins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D019013:CD40 Antigens; D018985:Epitopes, B-Lymphocyte; D007106:Immune Sera; D009596:Nitrophenols; D010648:Phenylacetates; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D005719:gamma-Globulins; C026242:4-hydroxy-5-nitrophenyl acetic acid