INTERNALIZATION OF THE 180 KDA BULLOUS PEMPHIGOID ANTIGEN AS IMMUNE-COMPLEXES IN BASAL KERATINOCYTES - AN IMPORTANT EARLY EVENT IN BLISTER FORMATION IN BULLOUS PEMPHIGOID
Y. Kitajima et al., INTERNALIZATION OF THE 180 KDA BULLOUS PEMPHIGOID ANTIGEN AS IMMUNE-COMPLEXES IN BASAL KERATINOCYTES - AN IMPORTANT EARLY EVENT IN BLISTER FORMATION IN BULLOUS PEMPHIGOID, British journal of dermatology, 138(1), 1998, pp. 71-76
We have previously shown that the 180 kDa bullous pemphigoid antigen (
BPAG2) is distributed on the lateral-apical (as a pool) and ventral (a
s hemidesmosomes) cell membranes of monolayer cultured keratinocytes a
nd-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 hemidesmo
somes on the ventral cell membrane, possibly by inhibiting the supply
of the antigen from the lateral-apical to the ventral membranes to for
m hemidesmosomes. The purpose of this paper is to examine, by using bi
opsy specimens from BP patients (12 cases), whether or not this intern
alization of BPAG2 is generated in situ. The fates of BPAG2, 230 kDa B
PA (BPAG1) and bound BP-IgG were traced by immunofluorescence microsco
py using monoclonal antibodies to BPAG1, BPAG2 and human IgG. In more
than half of the lesional and perilesional biopsy specimens, internali
zation of BPAG2 into the basal cells was observed, while in normal ski
n BPAG2 was detected on the whole surface of the basal cells without i
ts 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 complex
es of BPAG2 and BP-IgG may play an important part in blister formation
in BP.