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.