Abstract
Humoral immune responses are thought to be enhanced by complement-mediated recruitment of the CD21-CD19-CD81 coreceptor complex into the B cell antigen receptor (BCR) complex, which lowers the threshold of B cell activation and increases the survival and proliferative capacity of responding B cells. To investigate the role of the CD21-CD35 complement receptors in the generation of B cell memory, we analyzed the response against viral particles derived from the bacteriophage Qbeta in mice deficient in CD21-CD35 (Cr2(-/-)). Despite highly efficient induction of early antibody responses and germinal center (GC) reactions to immunization with Qbeta, Cr2(-/-) mice exhibited impaired antibody persistence paralleled by a strongly reduced development of bone marrow plasma cells. Surprisingly, antigen-specific memory B cells were essentially normal in these mice. In the absence of CD21-mediated costimulation, Qbeta-specific post-GC B cells failed to induce the transcriptional regulators Blimp-1 and XBP-1 driving plasma cell differentiation, and the antiapoptotic protein Bcl-2, which resulted in failure to generate the precursor population of long-lived plasma cells residing in the bone marrow. These results suggest that complement receptors maintain antibody responses by delivery of differentiation and survival signals to precursors of bone marrow plasma cells.
MeSH terms
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Allolevivirus / immunology
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Animals
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Antibodies, Viral / immunology
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Antibody Formation / genetics
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Antibody Formation / immunology
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Antigens, CD
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Antigens, Viral / immunology
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Apoptosis / genetics
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Apoptosis / immunology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology*
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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DNA-Binding Proteins / biosynthesis*
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DNA-Binding Proteins / immunology
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology*
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Mice
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Mice, Knockout
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Nuclear Proteins / biosynthesis*
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Nuclear Proteins / immunology
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Plasma Cells / immunology*
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Positive Regulatory Domain I-Binding Factor 1
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / immunology
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology
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Receptors, Complement 3d / genetics
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Receptors, Complement 3d / immunology*
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Regulatory Factor X Transcription Factors
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Repressor Proteins / biosynthesis*
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Repressor Proteins / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology
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Transcription Factors / biosynthesis*
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Transcription Factors / immunology
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X-Box Binding Protein 1
Substances
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Antibodies, Viral
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Antigens, CD
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Antigens, Viral
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DNA-Binding Proteins
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Nuclear Proteins
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Prdm1 protein, mouse
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, B-Cell
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Receptors, Complement 3d
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Regulatory Factor X Transcription Factors
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Repressor Proteins
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Transcription Factors
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X-Box Binding Protein 1
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Xbp1 protein, mouse
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Positive Regulatory Domain I-Binding Factor 1