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


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


CONCLUSIONS
Our data suggest that TACI dysfunction could contribute to the impaired antibody response to T-dependent antigens in common variable immunodeficiency.
Castigli
Emanuela
E
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Wilson
Stephen A
SA
Elkhal
Abdallah
A
Ozcan
Esra
E
Garibyan
Lilit
L
Geha
Raif S
RS
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology*; D002454:Cell Differentiation; D003564:Cytidine Deaminase / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis; D050835:Interferon Regulatory Factors / Q000235:genetics; D015847:Interleukin-4 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010950:Plasma Cells / Q000166:cytology*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000502:physiology*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000494:pharmacology; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099218:Interferon Regulatory Factor-4
D019013:CD40 Antigens; D003564:Cytidine Deaminase; D007073:Immunoglobulin E; D050835:Interferon Regulatory Factors; D015847:Interleukin-4; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D000099218:Interferon Regulatory Factor-4; C486361:Tnfrsf13b protein, mouse; C491959:Tnfsf13 protein, mouse
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