scholarly journals TACI and BAFF-R mediate isotype switching in B cells

2005 ◽  
Vol 201 (1) ◽  
pp. 35-39 ◽  
Author(s):  
Emanuela Castigli ◽  
Stephen A. Wilson ◽  
Sumi Scott ◽  
Fatma Dedeoglu ◽  
Shengli Xu ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Isotype Switching ◽  
B Cell Maturation ◽  
Human B Cells ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor family members BAFF and APRIL induce Ig isotype switching in human B cells. We analyzed the ability of BAFF and APRIL to induce isotype switching in murine B cells to IgG1, IgA, and IgE. APRIL and BAFF each engage two receptors, transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI) and B cell maturation antigen (BCMA), on B cells. In addition, BAFF engages a third receptor on B cells, BAFF-R. To determine the role of these receptors in isotype switching, we examined B cells from mice deficient in TACI, BCMA, and BAFF-R. The results obtained indicate that both TACI and BAFF-R are able to transduce signals that result in isotype switching.

scholarly journals Baff Binds to the Tumor Necrosis Factor Receptor–Like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population

2000 ◽  
Vol 192 (1) ◽  
pp. 129-136 ◽  
Author(s):  
Jeffrey S. Thompson ◽  
Pascal Schneider ◽  
Susan L. Kalled ◽  
LiChun Wang ◽  
Eric A. Lefevre ◽  
...  
Keyword(s):  
B Cells ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Cell Population ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

scholarly journals Maturation of Marginal Zone and Follicular B Cells Requires B Cell Activating Factor of the Tumor Necrosis Factor Family and Is Independent of B Cell Maturation Antigen

2001 ◽  
Vol 194 (11) ◽  
pp. 1691-1698 ◽  
Author(s):  
Pascal Schneider ◽  
Hisakazu Takatsuka ◽  
Anne Wilson ◽  
Fabienne Mackay ◽  
Aubry Tardivel ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Tumor Necrosis ◽  
Marginal Zone ◽  
Cell Maturation ◽  
Soluble Form ◽  
B Cell Maturation ◽  
B Cell Activating Factor ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

B cells undergo a complex series of maturation and selection steps in the bone marrow and spleen during differentiation into mature immune effector cells. The tumor necrosis factor (TNF) family member B cell activating factor of the TNF family (BAFF) (BLyS/TALL-1) plays an important role in B cell homeostasis. BAFF and its close homologue a proliferation-inducing ligand (APRIL) have both been shown to interact with at least two receptors, B cell maturation antigen (BCMA) and transmembrane activator and cyclophilin ligand interactor (TACI), however their relative contribution in transducing BAFF signals in vivo remains unclear. To functionally inactivate both BAFF and APRIL, mice transgenic for a soluble form of TACI were generated. They display a developmental block of B cell maturation in the periphery, leading to a severe depletion of marginal zone and follicular B2 B cells, but not of peritoneal B1 B cells. In contrast, mice transgenic for a soluble form of BCMA, which binds APRIL, have no detectable B cell phenotype. This demonstrates a crucial role for BAFF in B cell maturation and strongly suggests that it signals via a BCMA-independent pathway and in an APRIL-dispensable way.

scholarly journals Assembly and Regulation of the CD40 Receptor Complex in Human B Cells

1997 ◽  
Vol 186 (2) ◽  
pp. 337-342 ◽  
Author(s):  
Michelle R. Kuhné ◽  
Michael Robbins ◽  
John E. Hambor ◽  
Matthew F. Mackey ◽  
Yoko Kosaka ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
B Cells ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Receptor Complex ◽  
Tnf Receptor ◽  
B Cell Differentiation ◽  
Membrane Immunoglobulin ◽  
Human B Cells ◽  
Necrosis Factor

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily. Studies with human B cells show that the binding of CD154 (gp39, CD40L) to CD40 recruits TNF receptor– associated factor 2 (TRAF2) and TRAF3 to the receptor complex, induces the downregulation of the nonreceptor-associated TRAFs in the cell and induces an increased expression of Fas on the cell surface. Combined signaling through the interluekin 4 receptor and CD40 induces an increased expression of Fas with a commensurate increase in the level of TRAF2, but not TRAF3, that is recruited to the receptor complex. In contrast, engagement of the membrane immunoglobulin and CD40 limits Fas upregulation and reduces the recruitment of TRAF2, relative to TRAF3, to the CD40 receptor complex. These studies show that the TRAF composition of the CD40 receptor complex can be altered by signals that influence B cell differentiation.

scholarly journals A Soluble Form of B Cell Maturation Antigen, a Receptor for the Tumor Necrosis Factor Family Member April, Inhibits Tumor Cell Growth

2000 ◽  
Vol 192 (11) ◽  
pp. 1677-1684 ◽  
Author(s):  
Paul Rennert ◽  
Pascal Schneider ◽  
Teresa G. Cachero ◽  
Jeffrey Thompson ◽  
Luciana Trabach ◽  
...  
Keyword(s):  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Necrosis ◽  
Cell Maturation ◽  
Soluble Form ◽  
Tumor Cell Growth ◽  
B Cell Maturation ◽  
Necrosis Factor ◽  
B Cell Maturation Antigen

A proliferation-inducing ligand (APRIL) is a ligand of the tumor necrosis factor (TNF) family that stimulates tumor cell growth in vitro and in vivo. Expression of APRIL is highly upregulated in many tumors including colon and prostate carcinomas. Here we identify B cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), two predicted members of the TNF receptor family, as receptors for APRIL. APRIL binds BCMA with higher affinity than TACI. A soluble form of BCMA, which inhibits the proliferative activity of APRIL in vitro, decreases tumor cell proliferation in nude mice. Growth of HT29 colon carcinoma cells is blocked when mice are treated once per week with the soluble receptor. These results suggest an important role for APRIL in tumorigenesis and point towards a novel anticancer strategy.

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