By analysis with a panel of CD21 MoAbs it is shown that a large part o
f the soluble CD21 in human blood plasma is of the long isoform (CD21L
), as judged by comparison with antigen produced by mouse L cells tran
sfected with CD21L-cDNA and reactivity with the restricted CD21 MoAb R
4/23. This is compatible with the hypothesis that soluble CD21 in the
blood is mainly derived from follicular dendritic cells (FDC). Cells f
rom a human keratinocyte cell line transfected with cDNA from the Burk
itt lymphoma cell line Raji also produced soluble CD21L (sCD21L), wher
eas the short form of sCD21 (sCD21S) was the major component of sCD21
produced by the B lymphoblastoid cell line LICR-LON-HMy and the T cell
line Jurkat. Confocal studies of FDC isolated from human tonsil revea
led that CD21 was present in the cytoplasm. On gel filtration sCD21 fr
om untreated serum has an apparent size considerably greater than the
130 kD found by SDS-PAGE analysis. This may be partly accounted for by
the non-globular shape of the molecule, but may also indicate, as rep
orted by others, that in its native state sCD21 is complexed with othe
r proteins. However, no evidence of complexing with sCD23 or C3d could
be found.