| Autor: |
Kaji T; Laboratory for Immunological Memory, RIKEN Research Center for Allergy and Immunology, Tsurumi, Yokohama, Kanagawa 230-0045, Japan., Ishige A, Hikida M, Taka J, Hijikata A, Kubo M, Nagashima T, Takahashi Y, Kurosaki T, Okada M, Ohara O, Rajewsky K, Takemori T |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of experimental medicine [J Exp Med] 2012 Oct 22; Vol. 209 (11), pp. 2079-97. Date of Electronic Publication: 2012 Oct 01. |
| DOI: |
10.1084/jem.20120127 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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