complement receptors 1 and 2 in murine antibody responses to igm-complexed and uncomplexed sheep erythrocytes补体受体1和2在小鼠抗体反应igm-complexed和非复杂绵羊红细胞.pdfVIP

Complement Receptors 1 and 2 in Murine Antibody Responses to IgM-Complexed and Uncomplexed Sheep Erythrocytes 1 1 2 1 1 Christian Rutemark , Anna Bergman , Andrew Getahun , Jenny Hallgren , Frida Henningsson , Birgitta Heyman1* 1 Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden, 2 Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, Colorado, United States of America 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 Cr22/ 2 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 Cr22/ 2 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 su