Ie. Vandenherikoudijk et al., FUNCTIONAL-ANALYSIS OF HUMAN FC-GAMMA-RII (CD32) ISOFORMS EXPRESSED IN B-LYMPHOCYTES, The Journal of immunology, 152(2), 1994, pp. 574-585
The low affinity IgG receptor FcgammaRII (CD32) represents the most wi
dely distributed class of human FcgammaR. To analyze the biologic func
tions of different FcgammaRII isoforms, we stably transfected FcgammaR
IIb1, IIb1, IIb2, IIa, and a IIa tail- mutant to the mouse IIA1.6 B l
ymphoma cell line. Of these, FcgammaRIIb1 represents a receptor varia
nt that is identical to IIb1 except for a single amino acid difference
in the cytoplasmic tail (amino acid position 11) where a tyrosine (II
b1) is replaced by an aspartic acid (IIb1). Evaluation of capping abi
lity showed the FcgammaRIIb1 molecules to cap effectively, which was e
ven more apparent with IIb1. None of the FcgammaRIIa, IIa tail-, or I
Ib2 isoforms capped significantly. Internalization of FcgammaR-antibod
y complexes proved very efficient for both the FcgammaRIIa and IIb2 is
oforms, whereas the IIb1 molecules internalized moderately compared wi
th IIb1, which internalized less efficiently. Notably, human IgG aggr
egates were internalized effectively by FcgammaRIIa and moderately by
IIb2. Neither FcgammaRIIb1 nor IIb1 proved capable of internalizing s
uch IgG aggregates. Cross-linking of the different FcgammaR molecules
showed FcgammaRIIa capable of triggering increases in [Ca2+]i. Fcgamma
R expressed on B cells were able to down-regulate [Ca2+]i ion co-cross
-linking with sIgG. Notably, all three FcgammaRIIb receptors proved ac
tive in this respect, in contrast to FcgammaRIIa. The cell distributio
n of these FcgammaRII isoforms was analyzed in a panel of human B cell
lines to complement the IIA1.6 B cell model. FcgammaRIIa was found ex
pressed both at message and protein levels in all tested human B cell
lines. In the pre-B cell lines evaluated, no FcgammaRIIb molecules wer
e detectable, whereas both FcgammaRIIb1 and IIb2 molecules were found
present in more mature B cell lines. These data support both a complex
expression pattern of FcgammaRII isoforms in B cell lines and functio
nal differences between these B cell molecules.