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| Item Type: | Article |
|---|---|
| Title: | Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory |
| Creators Name: | Kaji, T., Ishige, A., Hikida, M., Taka, J., Hijikata, A., Kubo, M., Nagashima, T., Takahashi, Y., Kurosaki, T., Okada, M., Ohara, O., Rajewsky, K. and Takemori, T. |
| Abstract: | One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell-dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell-dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen. |
| Keywords: | Antibodies, B-Lymphocytes, DNA-Binding Proteins, DNA Sequence Analysis, Flow Cytometry, Gene Expression Profiling, Germ Cells, Germinal Center, Immunoglobulin G, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Immunologic Memory, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transgenic Mice, Animals, Mice |
| Source: | Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Volume: | 209 |
| Number: | 11 |
| Page Range: | 2079-2097 |
| Date: | 22 October 2012 |
| Official Publication: | https://doi.org/10.1084/jem.20120127 |
| PubMed: | View item in PubMed |
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