title: Defective B cell ontogeny and immune response in human complement receptor 2 (CR2, CD21) transgenic mice is partially recovered in the absence of C3.
abstract: Mice prematurely expressing human CR2 (hCR2) in the B cell lineage have a defective B cell ontogeny and immune response. Our recent analysis of this phenotype suggested that signaling through hCR2 and presumably mouse CD19 on the B cell surface, during bone marrow development, could result in the observed changes in B cell function in these mice. To test this hypothesis, we back crossed hCR2(high) transgenic mice onto the CD19(-/-) background. CD19(-/-)hCR2(high) mice were found to possess even fewer mature B cells than their CD19(+/+)hCR2(high) littermates, demonstrating that loss of CD19 exacerbated the effects elicited through hCR2. This data suggests that CD19 provides a survival signal during B cell development in this model. Next, we examined if the removal of the main ligand for CR2, namely C3d, through back-crossing onto the C3(-/-) background could restore normal B cell development. However, we found only minor recovery in peripheral B cell numbers and no obvious change in function. This was despite a three-fold increase in the level of hCR2 expression on B cells isolated from the spleen or bone marrow of C3(-/-)hCR2(high) mice when compared with C3 sufficient littermates. These data demonstrate that hCR2 is integrated in mouse B cell signaling and that the downstream effects of hCR2 expression during early B cell development are partially but not completely due to interaction with C3 fragments and signaling through CD19 in the bone marrow environment.
authors: Department of Medical Biochemistry & Immunology, Cardiff University, Heath Park, Cardiff CF14 4XX, UK.
authors: Jason
authors: J
authors: Twohig
authors: Liudmila
authors: L
authors: Kulik
authors: Catherine
authors: C
authors: Haluszczak
authors: Jason
authors: J
authors: Reuter
authors: Andreas
authors: A
authors: Rossbach
authors: Melanie
authors: M
authors: Bull
authors: V Michael
authors: VM
authors: Holers
authors: Kevin J
authors: KJ
authors: Marchbank
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology*; D003176:Complement C3 / Q000172:deficiency* / Q000235:genetics; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017464:Receptors, Complement 3d / Q000235:genetics*; D012756:Sheep
chemical_list: D003176:Complement C3; D017464:Receptors, Complement 3d