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

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.

• Authors: Emanuela Castigli, Stephen A Wilson, Abdallah Elkhal, Esra Ozcan, Lilit Garibyan, Raif S Geha
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 120 Issue 4 Pg. 885-91 (Oct 2007) ISSN: 0091-6749 [Print] United States
• PMID: 17689597 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CD40 Antigens
• Interferon Regulatory Factors
• Tnfrsf13b protein, mouse
• Tnfsf13 protein, mouse
• Transmembrane Activator and CAML Interactor Protein
• Tumor Necrosis Factor Ligand Superfamily Member 13
• interferon regulatory factor-4
• Interleukin-4
• Immunoglobulin E
• AICDA (activation-induced cytidine deaminase)
• Cytidine Deaminase

Topics

• Animals
• B-Lymphocytes (physiology)
• CD40 Antigens (physiology)
• Cell Differentiation
• Cytidine Deaminase (genetics)
• Immunoglobulin E (biosynthesis)
• Interferon Regulatory Factors (genetics)
• Interleukin-4 (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Plasma Cells (cytology)
• Transmembrane Activator and CAML Interactor Protein (physiology)
• Tumor Necrosis Factor Ligand Superfamily Member 13 (pharmacology)