title: Complement receptors 1 and 2 in murine antibody responses to IgM-complexed and uncomplexed sheep erythrocytes.
abstract: Early complement components are important for normal antibody responses. In this process, complement receptors 1 and 2 (CR1/2), expressed on B cells and follicular dendritic cells (FDCs) in mice, play a central role. Complement-activating IgM administered with the antigen it is specific for, enhances the antibody response to this antigen. Here, bone marrow chimeras between Cr2(-/-) and wildtype mice were used to analyze whether FDCs or B cells must express CR1/2 for antibody responses to sheep erythrocytes (SRBC), either administered alone or together with specific IgM. For robust IgG anti-SRBC responses, CR1/2 must be expressed on FDCs. Occasionally, weak antibody responses were seen when only B cells expressed CR1/2, probably reflecting extrafollicular antibody production enabled by co-crosslinking of CR2/CD19/CD81 and the BCR. When SRBC alone was administered to mice with CR1/2(+) FDCs, B cells from wildtype and Cr2(-/-) mice produced equal amounts of antibodies. Most likely antigen is then deposited on FDCs in a way that optimizes engagement of the B cell receptor, making CR2-facilitated signaling to the B cell superfluous. SRBC bound to IgM will have more C3 fragments, the ligands for CR1/2, on their surface than SRBC administered alone. Specific IgM, forming a complex with SRBC, enhances antibody responses in two ways when FDCs express CR1/2. One is dependent on CR1/2(+) B cells and probably acts via increased transport of IgM-SRBC-complement complexes bound to CR1/2 on marginal zone B cells. The other is independent on CR1/2(+) B cells and the likely mechanism is that IgM-SRBC-complement complexes bind better to FDCs than SRBC administered alone. These observations suggest that the immune system uses three different CR1/2-mediated effector functions to generate optimal antibody responses: capture by FDCs (playing a dominant role), transport by marginal zone B cells and enhanced B cell signaling.
authors: Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors: Christian
authors: C
authors: Rutemark
authors: Anna
authors: A
authors: Bergman
authors: Andrew
authors: A
authors: Getahun
authors: Jenny
authors: J
authors: Hallgren
authors: Frida
authors: F
authors: Henningsson
authors: Birgitta
authors: B
authors: Heyman
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D007114:Immunization; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000276:immunology*; D012756:Sheep
chemical_list: D007075:Immunoglobulin M; D017464:Receptors, Complement 3d