title: Molecular basis for a familial defect in phagocyte expression of IgG receptor I (CD64).
abstract: Four individuals have been identified, within a single family, who lack phagocyte expression of the high affinity type I IgG receptor (CD64). As a result, their monocytes are unable to support mouse IgG2a anti-CD3-induced T cell mitogenesis (nonresponder individuals). Southern blotting proved all three human Fc gamma receptor I (hFc gamma RI) genes to be present in nonresponders without major structural changes. Nucleotide sequencing showed identical hFc gamma RIA promoter regions in all individuals. At the message level, a distinct difference was noted between monocytes from control (responder) donors and from nonresponders. Both a 1.7- and 1.6-kb message were found in responders, whereas in nonresponders only the 1.6-kb species was detectable. Reverse transcriptase-PCR analyses showed the hFc gamma RIa transcript (encoding a receptor with three extracellular Ig-like domains) to be present at a approximately 15- to 20-fold lower level in nonresponder monocytes. Importantly, we found a single nucleotide difference (C --> T) within the extracellular domain exon 1-encoding region of hFc gamma RIA in nonresponders, resulting in the change of codon 92 (encoding an arginine) into a termination codon. This change likely affects mRNA stability and, thereby, leads to undetectable expression of phagocyte-hFc gamma RIa. Despite this defect, these individuals are apparently healthy, suggesting that hFc gamma RIa is dispensable for phagocyte functioning.
authors.affiliation: Department of Immunology, University Hospital Utrecht, The Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: van de Winkel
authors.forename: T P
authors.initials: TP
authors.lastname: de Wit
authors.forename: L K
authors.initials: LK
authors.lastname: Ernst
authors.forename: P J
authors.initials: PJ
authors.lastname: Capel
authors.forename: J L
authors.initials: JL
authors.lastname: Ceuppens
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*
chemical_list: D017452:Receptors, IgG; D012313:RNA; D004247:DNA