title: Mice expressing human CR1/CD35 have an enhanced humoral immune response to T-dependent antigens but fail to correct the effect of premature human CR2 expression.
abstract: We have previously demonstrated that mice expressing human complement receptor type 2 (CR2/CD21) during the CD43(+)/CD25(-) late pro-B cell stage of B cell development have marked changes in their subsequent B cell ontogeny. Here, we show that the humoral immune response to the T cell dependent antigen, sheep red blood cells (SRBCs) can be moderately enhanced with the addition of human CR1 (driven by the lambda promoter/enhancer transgene) to endogenous mCR1/CR2 expression on the B cell surface but that hCR1 expression alone (on the mouse CR1/2 deficient background) has no effect on the humoral immune response or general B cell development. Furthermore, expression of hCR1 had no recuperative effect on the markedly altered B cell phenotype noted with premature expression of hCR2 (either in the presence or absence of endogenous mCR1/2). We conclude that hCR1 alone cannot replace the role of CR2 in mice and that the effects of premature hCR2 expression during BCR development are not significantly altered by the addition of hCR1 at that developmental stage or beyond; thus hCR2 signaling in the mouse remains dominant over subsequent input from either hCR1 or endogenous receptors.
authors.affiliation: Applied Immunobiology and Transplantation, Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle-upon-Tyne, UK.
authors.forename: Isabel Y
authors.initials: IY
authors.lastname: Pappworth
authors.forename: Christine
authors.initials: C
authors.lastname: Hayes
authors.forename: Jason
authors.initials: J
authors.lastname: Dimmick
authors.forename: B Paul
authors.initials: BP
authors.lastname: Morgan
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Marchbank
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D018858:Germinal Center / Q000276:immunology; D056724:Immunity, Humoral; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017463:Receptors, Complement 3b / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D019076:Transgenes
chemical_list: C509991:CR1 protein, human; D017463:Receptors, Complement 3b