title: Mouse complement receptors type 1 (CR1;CD35) and type 2 (CR2;CD21): expression on normal B cell subpopulations and decreased levels during the development of autoimmunity in MRL/lpr mice.
abstract: Human complement receptors type 1 (hCR1;CD35) and type 2 (hCR2;CD21) are expressed on B lymphocytes at specific stages during differentiation and activation. These receptors play critical roles in the immune response to T-dependent Ags in addition to germinal center formation. Expression of both hCR2 and hCR1 is decreased on B lymphocytes of patients with systemic lupus erythematosus (SLE). We have studied the expression of mouse CR2 and CR1 on normal populations of mouse B lymphocytes in BALB/c mice. Our results demonstrate that expression of these receptors in the normal state closely parallels that of hCR2. During bone marrow development, expression is first detected on low B220/high IgM cells, demonstrating that complement receptors appear after central tolerance mechanisms are completed. In the splenic microenvironment the highest levels of receptor expression are found on marginal zone B lymphocytes. Mouse CR2 and CR1 are also found on peritoneal B1a and B1b cells in addition to IgA+ Peyer's patch B cells. Activation of splenic B cells under Th2 conditions results in a marked decrease in receptor expression. To determine whether the patterns of receptor expression also parallel those found in human disease, we studied the MRL lpr/lpr (MRL/lpr) model of SLE. Interestingly, we found an early decrease in complement receptor expression that is progressive and first detectable before major clinical manifestations of nephritis. We hypothesize that the early decrease in complement receptor expression such as that demonstrated by MRL/lpr mice plays an important role in the pathogenesis of murine and perhaps human SLE.
authors.affiliation: Department of Pathology, University of Iowa School of Medicine, Iowa City 52242, USA.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Kozono
authors.forename: T J
authors.initials: TJ
authors.lastname: Waldschmidt
authors.forename: D
authors.initials: D
authors.lastname: Berthiaume
authors.forename: R J
authors.initials: RJ
authors.lastname: Quigg
authors.forename: A
authors.initials: A
authors.lastname: Baron
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells; D007134:Immunoglobulin Switch Region; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D010529:Peritoneal Cavity / Q000166:cytology; D017463:Receptors, Complement 3b / Q000096:biosynthesis*; D017464:Receptors, Complement 3d / Q000096:biosynthesis*; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology
chemical_list: D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d