Mouse germinal center B cells with the xid mutation retain responsiveness to anti-mouse CD40 antibodies but diminish IL-5 responsiveness

The germinal center (GC) develops in secondary lymphoid tissues in response to thymus-dependent (TD) antigens, To investigate the molecular mechanism of a cell differentiation in GC, we enriched GC a cells from spleen of TD antigen-immunized wild-type and X-linked immunodeficient (XID) mice, and examined the differentiation of QC B cells into antigen-specific IgG1 antibody-forming cells (AFC) in response to anti-CD40 mAb and cytokines, A significant proportion of freshly purified GC a cells expressed receptors for IL-4 and IL-5, Anti-CD40 mAb sustained the viability of GC a cells and IL-4 co-operated with anti-CD40 mAb for further enhancement of the cell viability, Anti-CD40 mAb and IL-4 were essential for inducing differentiation of GC a cells into antigen-specific IgG1-AFC and IL-5 efficiently enhanced their differentiation, GC B cells with the rid mutation responded for proliferation to CD40 ligation to a lesser extent and for the IgG1-AFC response to anti-CD40 mAb together with IL-4, but they showed impaired responsiveness to IL-5, regardless of enhanced expression of IL-5R in response to anti-CD40 mAb and IL-4, These results suggest that anti-CD40 mAb, IL-4 and IL-5 play a critical role in the differentiation of mouse GC a cells, The GC a cells from XID mice show a functional defect with respect to IL-5-mediated differentiation.