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Optimal germinal center B cell activation and T-dependent antibody responses require expression of the mouse complement receptor Cr1.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2013 Jul 01; Vol. 191 (1), pp. 434-47. Date of Electronic Publication: 2013 Jun 03. - Publication Year :
- 2013
-
Abstract
- Follicular dendritic cells (FDCs) and complement receptor (Cr)1 and complement receptor (Cr)2 are important for the generation of humoral immunity. Cr1/2 expression on B cells and FDCs was shown to provide a secondary signal for B cell activation, to facilitate transport of Ag in immune follicles, and to enhance retention of immune complexes by FDCs. We show in this study that murine B cells predominantly express the Cr2 product from the Cr2 gene, whereas FDCs almost exclusively express the Cr1 isoform generated from the Cr2 gene. To define the specific role of Cr1, we created an animal that maintains normal cell-restricted expression of Cr2 but does not express Cr1. Cr1-deficient (Cr1KO) mice develop normal B1 and B2 immature and mature B cell subsets and have normal levels of naive serum Abs but altered levels of natural Abs. Immunization of the Cr1KO animal demonstrates deficient Ab responses to T-dependent, but not T-independent, Ags. Germinal centers from the immunized Cr1KO animal possess a deficiency in activated B cells, similar to that seen for animals lacking both Cr1 and Cr2 or C3. Finally, animals lacking only Cr1 respond similarly to wild-type animals to infections with Streptococcus pneumoniae, a pathogen to which animals lacking C3 or both Cr1 and Cr2 are particularly sensitive. Altogether, these data suggest that the production of Cr1, primarily by FDCs, is critical in the generation of appropriately activated B cells of the germinal center and the generation of mature Ab responses.
- Subjects :
- Animals
B-Lymphocyte Subsets metabolism
Dendritic Cells, Follicular immunology
Dendritic Cells, Follicular metabolism
Female
Gene Expression Regulation immunology
Germinal Center cytology
Immunoglobulin M genetics
Lymphocyte Activation genetics
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Protein Isoforms biosynthesis
Protein Isoforms genetics
Receptors, Complement 3b deficiency
Receptors, Complement 3b immunology
Receptors, Complement 3d genetics
Receptors, Complement 3d immunology
Streptococcus pneumoniae immunology
T-Lymphocyte Subsets metabolism
T-Lymphocyte Subsets microbiology
B-Lymphocyte Subsets immunology
Germinal Center immunology
Immunoglobulin M biosynthesis
Lymphocyte Activation immunology
Receptors, Complement 3b genetics
Receptors, Complement 3d biosynthesis
T-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 191
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 23733878
- Full Text :
- https://doi.org/10.4049/jimmunol.1203176