Reference - Detail
RRC ID | 18535 |
---|---|
Author | Kaji T, Ishige A, Hikida M, Taka J, Hijikata A, Kubo M, Nagashima T, Takahashi Y, Kurosaki T, Okada M, Ohara O, Rajewsky K, Takemori T. |
Title | Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. |
Journal | J Exp Med |
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. |
Volume | 209(11) |
Pages | 2079-97 |
Published | 2012-10-22 |
DOI | 10.1084/jem.20120127 |
PII | jem.20120127 |
PMID | 23027924 |
PMC | PMC3478929 |
MeSH | Animals Antibodies / genetics Antibodies / immunology* Antibodies / metabolism B-Lymphocytes / immunology* B-Lymphocytes / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / immunology DNA-Binding Proteins / metabolism Female Flow Cytometry Gene Expression Profiling Germ Cells / immunology* Germ Cells / metabolism Germinal Center / immunology* Germinal Center / metabolism Immunoglobulin G / genetics Immunoglobulin G / immunology Immunoglobulin G / metabolism Immunoglobulin Heavy Chains / genetics Immunoglobulin Heavy Chains / immunology Immunoglobulin Heavy Chains / metabolism Immunoglobulin Variable Region / genetics Immunoglobulin Variable Region / immunology Immunoglobulin Variable Region / metabolism Immunologic Memory / immunology* Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Molecular Sequence Data Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins c-bcl-6 Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Signal Transduction / genetics Signal Transduction / immunology* |
IF | 11.743 |
Times Cited | 145 |
WOS Category | MEDICINE, RESEARCH & EXPERIMENTAL IMMUNOLOGY |
Resource | |
Mice | RBRC01834 RBRC01835 |