Activation of HLA-A2-specific memory B cells in severe combined immunodeficient mice.
Peripheral blood leukocytes of all five HLA-A2-sensitized patients produced significant levels of human IgG (> or = 0.25 micrograms/ml) following polyclonal activation in vitro, but PBLs from only one patient (K.H.) who had been transfused recently (< 4 weeks) produced detectable anti-HLA-A2 IgG. PBLs from this in vitro responder and from one in vitro nonresponder (L.G.) were transferred intraperitoneally into SCID mice. A low level (range, 5-40 ng/ml) of human anti-HLA-A2 IgG was detected in the serum of the mice without additional stimulation. This anti-HLA-A2 IgG response was boosted (range, 40-200 ng/ml) when mice received a human skin xenograft or an early challenge with x-irradiated human leukocytes intraperitoneally. Although the anti-HLA antibodies produced were specific for HLA-A2, the boosting of anti-HLA-A2 IgG production did not require the expression of the HLA-A2 protein, since either HLA-A2-negative skin xenografts or HLA-identical x-irradiated PBLs enhanced the production of anti-HLA-A2 IgG. Dose-response of transferred PBLs and kappa:lambda composition of individual mouse anti-HLA-A2 production suggested that low-frequency human memory B-cell clones were stimulated to proliferate and/or triggered to become high Ab secretors by skin graft or PBL boost.
Department of Surgery, University of Wisconsin, Madison 53792.
T
T
Niguma
L D
LD
DeVito
A P
AP
Grailer
J H
JH
Fechner
H W
HW
Sollinger
W J
WJ
Burlingham
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID
D015789:HLA-A2 Antigen; D007074:Immunoglobulin G