Internalization of the 180 kDa bullous pemphigoid antigen as immune complexes in basal keratinocytes: an important early event in blister formation in bullous pemphigoid.
We have previously shown that the 180 kDa bullous pemphigoid antigen (BPAG2) is distributed on the lateral-apical (as a pool) and ventral (as hemidesmosomes) cell membranes of monolayer cultured keratinocytes and that addition of IgG purified from bullous pemphigoid (BP) patients (BP-IgG) causes the internalization of immune complexes of BPAG2 and BP-IgG from the lateral-apical cell membrane. This internalization of BPAG2 is believed to inhibit the Ca2+ induced reformation of hemidesmosomes on the ventral cell membrane, possibly by inhibiting the supply of the antigen from the lateral-apical to the ventral membranes to form hemidesmosomes. The purpose of this paper is to examine, by using biopsy specimens from BP patients (12 cases), whether or not this internalization of BPAG2 is generated in situ. The fates of BPAG2, 230 kDa BPA (BPAG1) and bound BP-IgG were traced by immunofluorescence microscopy using monoclonal antibodies to BPAG1, BPAG2 and human IgG. In more than half of the lesional and perilesional biopsy specimens, internalization of BPAG2 into the basal cells was observed, while in normal skin BPAG2 was detected on the whole surface of the basal cells without its internalization. No internalization of BPAG1 was detected in BP and normal epidermis. These results suggest that binding of BP-IgG on the lateral-apical cell surface of basal cells causes internalization of BPAG2 in situ in the epidermis of BP patients similar to that seen in cultured cell systems, and that this internalization of immune complexes of BPAG2 and BP-IgG may play an important part in blister formation in BP.
Kitajima
Y
Y
Department of Dermatology, Gifu University School of Medicine, Japan.
Nojiri
M
M
Yamada
T
T
Hirako
Y
Y
Owaribe
K
K
D000368:Aged; D000369:Aged, 80 and over; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D004817:Epidermis / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000378:metabolism*; D013997:Time Factors; D000097805:Collagen Type XVII
D000936:Antigen-Antibody Complex; D001324:Autoantigens; D002352:Carrier Proteins; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII; C486268:DST protein, human