Antibody-forming cell induction during an early phase of germinal centre development and its delay with ageing

The present study was initiated to determine if an early phase of germinal centre (GC) development is associated with the generation of antibody-forming cells (AFC). Germinal centres in draining lymph nodes from immune mice were examined histochemically after secondary immunization for the presence of AFC at both the light and electron microscopic levels. Additionally, peanut agglutinin (PNA) high (Hi) GC B cells were isolated, placed in cell culture and specific antibody production was monitored at successive intervals. Electron microscopy showed that plasma cells in all stages of differentiation were present within GC at 3-5 days and to a lesser extent at 7 days following antigenic challenge. Furthermore, PNAHi GC B cells obtained between Days 3 and 5 spontaneously produced specific IgG when placed in culture. Germinal centre B cells isolated either before or after this period did not produce antibody without the addition of T-cell cytokines. Induction of AFC in GC occurred at the time when GC B cells acquire follicular dendritic cell (FDC)-derived, immune complex-coated bodies (iccosomes) and process and present this antigen to helper T cells. This suggested a causal relationship between iccosome release and AFC induction. Support for this was obtained by examination of AFC induction in aged mice where iccosome release has not been observed. Peanut agglutinin-positive GC B cells isolated from aged mice on Days 3-5 after antigen challenge failed to spontaneously produce specific antibody. Collectively, these data show that GC development 3-5 days after booster immunization results in AFC generation and suggests a role for FDC iccosomes in their induction.