Complement receptors 1 and 2 influence the immune environment in a B cell receptor-independent manner.
The CD21/35 proteins are complement receptors implicated in controlling and interpreting activation states of the innate and acquired immune responses. One defect of CD21/35(-/-) animals is depressed production of Ag-specific IgG3 which we show is evident in vivo but not in vitro. Gene expression profiles obtained from naive wild-type and CD21/35(-/-) splenocytes demonstrated enhanced expression of inflammatory mediators from CD11b(+) splenocytes in the CD21/35(-/-) animals. Splenocyte populations between wild-type and CD21/35(-/-) mice were similar except for a moderate increase in GR1(low)CD31(+) immature myeloid cells. Furthermore, depletion of neutrophils and other GR1-expressing cells alleviates elevated inflammatory gene expression in the CD21/35(-/-) spleen. Complement activation also plays a key role in the differential gene expression observed in the CD21/35-deficient mouse as depletion of C3 or inhibition of C3a receptor signaling within the animal returned inflammatory gene expression within the spleen to wild-type levels. Finally, C3 depletion before immunization allowed for the enhanced production of Ag-specific IgG3 production in the CD21/35(-/-) mouse compared with mock-depleted animals. These data suggest that the overall environment of the CD21/35(-/-) spleen is quite different from that of the wild-type animal perhaps due to altered complement convertase activity. This difference may be responsible for a number of the phenotypes ascribed to the deficiency of CD21/35 proteins on B cells and follicular dendritic cells.
Jacobson
Amanda C
AC
Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
Weis
Janis J
JJ
Weis
John H
JH
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011951:Receptors, Complement / Q000276:immunology*; D017463:Receptors, Complement 3b / Q000276:immunology; D017464:Receptors, Complement 3d / Q000276:immunology; D013154:Spleen / Q000378:metabolism
D000906:Antibodies; D000941:Antigens; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d