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J Allergy Clin Immunol. 2007 Oct;120(4):885-91. Epub 2007 Aug 8.

Transmembrane activator and calcium modulator and cyclophilin ligand interactor enhances CD40-driven plasma cell differentiation.

Author information

1
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.

Abstract

BACKGROUND:

Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a receptor used by B cell-activating factor of the TNF family and a proliferation-inducing ligand (APRIL) to induce isotype switching independently of CD40 and is mutated in patients with common variable immunodeficiency.

OBJECTIVE:

We sought to determine whether TACI and CD40 cooperate in inducing class switch recombination and immunoglobulin production.

METHODS:

Naive mouse B cells were stimulated with suboptimal concentrations of anti-CD40 plus IL-4 in the presence or absence of APRIL or anti-TACI. IgG(1) and IgE production was measured by means of ELISA. mRNA for Cgamma(1) and Cepsilon germ-line transcripts, activation-induced cytidine deaminase, and mature gamma(1) and epsilon transcripts were measured by means of RT-PCR. Plasmablasts were enumerated by using syndecan-1/CD138 staining. Interferon regulatory factor 4, B lymphocyte-induced maturation protein 1, and IL6 mRNA expression was measured by using quantitative PCR.

RESULTS:

TACI ligation enhanced IgG(1) and IgE secretion by naive murine B cells stimulated by anti-CD40 plus IL-4, with little effect on B-cell proliferation or class switch recombination. In contrast, TACI ligation of anti-CD40 plus IL-4-stimulated B cells induced a significant increase in syndecans-1/CD138-positive cells. TACI ligation caused a modest but significant increase in the expression of interferon regulatory factor 4, with no detectable change in B lymphocyte-induced maturation protein 1 expression.

CONCLUSION:

TACI and CD40 signaling converge to promote B-cell differentiation into plasmablasts.

CLINICAL IMPLICATIONS:

Our data suggest that TACI dysfunction could contribute to the impaired antibody response to T-dependent antigens in common variable immunodeficiency.

PMID:
17689597
PMCID:
PMC2121612
DOI:
10.1016/j.jaci.2007.06.012
[Indexed for MEDLINE]
Free PMC Article
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