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Fc RIIIB Gene Duplication: Evidence for Presence and
Expression of Three Distinct Fc RIIIB Genes in
NA(1+,2+)SH(+) Individuals
Harry R. Koene,
Marion Kleijer,
Dirk Roos,
Masja de Haas, and
Albert E.G.Kr. Von dem Borne
From the Central Laboratory of the Netherlands Red Cross Blood
Transfusion Service and Laboratory for Clinical and Experimental
Immunology, Academic Medical Center, University of Amsterdam,
Amsterdam, The Netherlands and the Department of Hematology, Academic
Medical Center, Amsterdam, The Netherlands.
Recently, a new alloantigen on IgG Fc receptor type IIIb
(Fc RIIIb), SH, was described (Bux et al, Blood 89:1027,
1997). We identified three healthy individuals whose neutrophils
reacted positively with the SH antiserum. The neutrophil antigen (NA) phenotype of all three donors was NA(1+,2+). Analysis of genomic DNA showed that the three donors were positive for the described SH-encoding mutation in the NA2-Fc RIIIB gene,
266C A. However, NA(1,2) genotyping and nucleotide sequencing
of an NA2-specific fragment amplified from the genomic DNA
fragment showed that these individuals carried three Fc RIIIB
genes, namely, NA1-Fc RIIIB, NA2-Fc RIIIB, and
SH-Fc RIIIB, encoding NA1-Fc RIIIb, NA2-Fc RIIIb, and
SH-Fc RIIIb, respectively. Southern blot analysis confirmed these
findings. Furthermore, all three transcripts were isolated from
neutrophil mRNA. To investigate whether the presence of three Fc RIIIB genes resulted in a higher membrane expression of
Fc RIIIb, we measured the reactivity of neutrophils from
NA(1+,2+)SH(+) individuals with a panel of CD16 monoclonal
antibodies (MoAbs) in comparison with neutrophils from
NA(1+,2+)SH( ) controls. Reactivity of four different
anti-pan-Fc RIII MoAbs and NA2-specific MoAb GRM1 was higher with
SH(+) neutrophils compared with controls, whereas that of
NA1-specific MoAbs was similar, which is in concordance with the
results from the genomic analysis. We observed that reactivity with
NA2-specific CD16 MoAb PEN1 was sixfold higher in SH(+) individuals compared with controls. Apparently, the 60Ala Asp substitution in SH-Fc RIIIb influences the epitope recognized by PEN1. In
conclusion, we identified three NA(1+,2+)SH(+) individuals
carrying three Fc RIIIB genes and observed a clear
gene-dosage effect on the level of expression of neutrophil Fc RIIIb.
Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 673-679
© 1998 by The American Society of Hematology.

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