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Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory

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Official URL:https://doi.org/10.1084/jem.20120127
PubMed:View item in PubMed
Creators Name:Kaji, T. and Ishige, A. and Hikida, M. and Taka, J. and Hijikata, A. and Kubo, M. and Nagashima, T. and Takahashi, Y. and Kurosaki, T. and Okada, M. and Ohara, O. and Rajewsky, K. and Takemori, T.
Journal Title:Journal of Experimental Medicine
Journal Abbreviation:J Exp Med
Volume:209
Number:11
Page Range:2079-2097
Date:22 October 2012
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
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.
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Item Type:Article

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