B cells from mice prematurely expressing human complement receptor type 2 are unresponsive to T-dependent antigens.
Complement receptor type 2 (CR2/CD21), in association with CD19, plays an important role in enhancing mature B cell responses to opsonized Ags. We have shown that mice expressing a human CR2/CD21 (hCR2/CD21) transgene during the CD43(+)/CD25(-) late pro-B cell stage of B cell development demonstrate marked changes in subsequent B cell ontogeny. In the present study, we show that the humoral immune response to the T cell-dependent Ag, sheep RBC, is muted severely in a manner inversely proportional to B cell expression level of hCR2. Individual Ag-specific IgG isotypes vary in the degree to which they are affected but all are reduced while IgM titers are normal. A substantial reduction in germinal centers, both in size and frequency, in the spleens of immunized hCR2 transgenic mice demonstrates a failure to maintain germinal center reaction. However, both IgM expression levels and LPS-proliferative responses appear fully intact in B cells from hCR2-positive mice, suggesting that this alteration in B cell phenotype is different qualitatively from that of specific Ag-defined anergy models. These data suggest that the unresponsiveness to T-dependent Ags displayed by hCR2-positive B cells is linked to an increase in the level of stimulus required to propel the B cell into a fully activated state and thus a normal humoral immune response to Ags. We conclude that this phenotype and these mice may offer an additional means to dissect mechanisms underlying B cell tolerance and Ag responsiveness both in bone marrow and periphery.
Birrell
Louise
L
Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, UK.
Kulik
Liudmila
L
Morgan
B Paul
BP
Holers
V Michael
VM
Marchbank
Kevin J
KJ
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017635:Clonal Anergy / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017464:Receptors, Complement 3d / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics*; D012756:Sheep; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D008070:Lipopolysaccharides; D017464:Receptors, Complement 3d