Reference - Detail
|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|
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.
|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*|
|WOS Category||MEDICINE, RESEARCH & EXPERIMENTAL IMMUNOLOGY|
|Mice||B6-Tg(CAG-FLPe)36 (RBRC01834) B6-Tg(CAG-FLPe)37 (RBRC01835)|