The role of complement receptors in production of antibodies specific for Galalpha1,3Gal.
By using alpha-galactosyl transferase knockout (GT-/-) mice, which make natural alphaGal-reactive antibodies, we examined the role of complement receptors in the production of alphaGal-specific antibodies. GT-/- mice were crossed with complement receptor 2 loci knockout mice to generate double knockout (DKO) mice. alphaGal-specific natural antibodies were detectable by enzyme-linked immunosorbent assay in the serum of GT-/- mice by 9 weeks of age. In contrast, only low titers of alphaGal-specific natural antibodies were detectable only in the serum of older DKO mice. Serum titers of alphaGal-reactive antibodies in GT-/- mice increased significantly after immunization with pig cells. In contrast, immunization had little effect on alphaGal-reactive antibody levels in DKO mice. Similarly, pretreatment of GT-/- mice with a blocking antibody to CD21 and CD35 inhibited production of alphaGal-reactive antibodies after immunization. However, DKO mice were able to make alphaGal-specific antibodies after secondary immunization. Thus, Cr2 loci-encoded receptors seem to be directly involved in the production of primary alphaGal-reactive antibodies.
Kaye
Joel
J
Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Building 149, 13th Street, Boston, MA 02129, USA.
Bagley
Jessamyn
J
Malkowski
Denise
D
Iacomini
John
J
D000818:Animals; D000918:Antibody Specificity; D004187:Disaccharides / Q000378:metabolism*; D000939:Epitopes / Q000032:analysis; D005700:Galactosyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011951:Receptors, Complement / Q000276:immunology*; D017464:Receptors, Complement 3d / Q000276:immunology*; D013552:Swine; D014183:Transplantation, Heterologous
D004187:Disaccharides; D000939:Epitopes; D011951:Receptors, Complement; D017464:Receptors, Complement 3d; C055075:galactosyl-(1-3)galactose; D005700:Galactosyltransferases