Productive follicular dendritic cell (FDC)-B cell interactions appear to in
volve critical ligand-receptor interactions. Immune complexes (IC) on FDC a
ctivate complement and provide FDC with a complement-derived CD21 ligand (C
D21L), which bind CD21, while antigen in the IC binds on the B cell-BCR. Fu
rther, FDC-Fc gamma RIIB binds Fc regions of antibodies in IC and reduces c
oligation of BCR and Fc gamma RIIB minimizing an inhibitor of B cell activa
tion. Given that Fc receptors and complement receptors bind immunoglobulins
and complement fragments of other species, we reasoned that FDC accessory
activity should cross MHC and species barriers. This prediction was tested
using memory lymphocytes from OVA-immune mice and TT-immune humans in combi
nation with FDC from murine lymph nodes and human tonsils. Human and murine
FDC converted le into potent immunogens (specific antibody increased from
background to thousands of ng/ml). MHC barriers did not restrict this activ
ity and human FDC worked with murine lymphocytes and murine FDC worked with
human lymphocytes. Furthermore, stimulation via MHC-dependent allogeneic o
r zenogeneic mechanisms did not promote antibody production by FDC. Polyclo
nal responses stimulated by lipopolysaccharide and pokeweed mitogen were al
so promoted (10-100-fold) and anti-CD21 blocked FDC activity. These results
substantiate the hypothesis that FDC are necessary for strong recall respo
nses and that FDC-CD21L is critical.