IL-7 Enables Antibody Responses to Bacterial Polysaccharides by Promoting B Cell Receptor Diversity

The Journal of Immunology : Official Journal of the American Association of Immunologists
Gregory S DickinsonKishore R Alugupalli

Abstract

Polysaccharide vaccines such as the Vi polysaccharide (ViPS) of Salmonella enterica serovar Typhi induce efficient Ab responses in adults but not in young children. The reasons for this difference are not understood. IL-7 dependency in B cell development increases progressively with age. IL-7Rα-mediated signals are required for the expression of many VH gene segments that are distal to DH-JH in the IgH locus and for the complete diversification of the BCR repertoire. Therefore, we hypothesized that B cells generated in the absence of IL-7 do not recognize a wide range of Ags because of a restricted BCR repertoire. Compared with adult wildtype mice, young wildtype mice and IL-7-deficient adult mice generated a significantly reduced Ab response to ViPS. Additionally, ViPS-binding B cells in adult wildtype mice predominantly used distal VH gene segments. Transgenic expression of either IL-7 or a BCR encoded by a distal VH gene segment permitted young mice to respond efficiently to bacterial polysaccharides. These results indicate that restricted VH gene usage early in life results in a paucity of Ag-specific B cell precursors, thus limiting antipolysaccharide responses.

References

Aug 1, 1988·The Journal of Experimental Medicine·H D Jeong, J M Teale
Jul 14, 1972·Science·B BlombergM Weigert
Jan 1, 1983·The Journal of Experimental Medicine·B NewmanL Hood
Apr 1, 1995·The Journal of Experimental Medicine·U von Freeden-JeffryR Murray
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·C WeiI Goldschneider
Mar 3, 2001·Current Opinion in Immunology·F Martin, J F Kearney
May 24, 2001·Immunity·G U von BülowR J Bram
Oct 17, 2001·The Journal of Experimental Medicine·T L CarvalhoP Vieira
Nov 12, 2003·The Journal of Experimental Medicine·Ewa SitnickaSten Eirik W Jacobsen
Sep 11, 2004·Immunity·Kishore R AlugupalliRachel M Gerstein
Dec 14, 2004·Immunologic Research·Cheri D LandersSubbarao Bondada
Aug 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Goutam SenClifford M Snapper
Jan 18, 2006·JAMA : the Journal of the American Medical Association·Dominic F KellyE Richard Moxon
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vanessa Sancho-Shimizu, Danielle Malo
Jul 11, 2006·BMJ : British Medical Journal·Zulfiqar A Bhutta
Nov 9, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kazu Kikuchi, Motonari Kondo
Jan 30, 2007·Nature Reviews. Immunology·Renata Mazzucchelli, Scott K Durum
Nov 24, 2007·Cellular Microbiology·R Paul WilsonAndreas J Bäumler
Dec 18, 2007·Current Topics in Microbiology and Immunology·K R Alugupalli
Jun 20, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cheng-Ran XuAnn J Feeney
Jul 9, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sunita KanswalMustafa Akkoyunlu
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ikuko ToriiHiromi Kubagawa
Mar 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasmin Khan ParrishKimberly J Payne
Oct 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jeremy B Foote, John F Kearney
Dec 18, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·John A Crump, Eric D Mintz
May 28, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne K ShrinerKishore R Alugupalli

❮ Previous
Next ❯

Citations

Nov 23, 2019·Cell and Tissue Research·Morteza HeidarzadehReza Rahbarghazi

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.