TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen

Shoichiro Tsuji, Lucas Stein, Nobuhiko Kamada, Gabriel Nuñez, Richard J Bram, Bruce A. Vallance, Ana E. Sousa, Jeffrey L. Platt, Marilia Cascalho

Research output: Contribution to journalArticle

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Abstract

The transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) controls differentiation of long-lived plasma cells, and almost 10% of individuals with common variable immunodeficiency (CVID) express either the C104R or A181E variants of TACI. These variants impair TACI function, and TACI-deficient mice exhibit a CVID-like disease. However, 1%-2% of normal individuals harbor the C140R or A181E TACI variants and have no outward signs of CVID, and it is not clear why TACI deficiency in this group does not cause disease. Here, we determined that TACI-deficient mice have low baseline levels of Ig in the blood but retain the ability to mutate Ig-associated genes that encode antigen-specific antibodies. The antigen-specific antibodies in TACI-deficient mice were produced in bursts and had higher avidity than those of WT animals. Moreover, mice lacking TACI were able to clear Citrobacter rodentium, a model pathogen for severe human enteritis, more rapidly than did WT mice. These findings suggest that the high prevalence of TACI deficiency in humans might reflect enhanced host defense against enteritis, which is more severe in those with acquired or inherited immunodeficiencies.

Original languageEnglish (US)
Pages (from-to)4857-4866
Number of pages10
JournalJournal of Clinical Investigation
Volume124
Issue number11
DOIs
StatePublished - Nov 3 2014

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Antibody Affinity
Common Variable Immunodeficiency
Enteritis
Citrobacter rodentium
Cyclophilins
Antigens
Immunoglobulin Genes
Antibodies
Plasma Cells
Ligands
Calcium

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Tsuji, S., Stein, L., Kamada, N., Nuñez, G., Bram, R. J., Vallance, B. A., ... Cascalho, M. (2014). TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen. Journal of Clinical Investigation, 124(11), 4857-4866. https://doi.org/10.1172/JCI74428

TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen. / Tsuji, Shoichiro; Stein, Lucas; Kamada, Nobuhiko; Nuñez, Gabriel; Bram, Richard J; Vallance, Bruce A.; Sousa, Ana E.; Platt, Jeffrey L.; Cascalho, Marilia.

In: Journal of Clinical Investigation, Vol. 124, No. 11, 03.11.2014, p. 4857-4866.

Research output: Contribution to journalArticle

Tsuji, S, Stein, L, Kamada, N, Nuñez, G, Bram, RJ, Vallance, BA, Sousa, AE, Platt, JL & Cascalho, M 2014, 'TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen', Journal of Clinical Investigation, vol. 124, no. 11, pp. 4857-4866. https://doi.org/10.1172/JCI74428
Tsuji, Shoichiro ; Stein, Lucas ; Kamada, Nobuhiko ; Nuñez, Gabriel ; Bram, Richard J ; Vallance, Bruce A. ; Sousa, Ana E. ; Platt, Jeffrey L. ; Cascalho, Marilia. / TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 11. pp. 4857-4866.
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