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BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population.

Thompson JS, Schneider P, Kalled SL, Wang L, Lefevre EA, Cachero TG, MacKay F, Bixler SA, Zafari M, Liu ZY, Woodcock SA, Qian F, Batten M, Madry C, Richard Y, Benjamin CD, Browning JL, Tsapis A, Tschopp J, Ambrose C - J. Exp. Med. (2000)

Bottom Line: 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.These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Biogen, Incorporated, Cambridge, Massachusetts 02142, USA.

ABSTRACT
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.

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Related in: MedlinePlus

Administration of BCMA-Ig reduces the peripheral B cell population. Adult Balb/c mice were treated with four intraperitoneal injections of BCMA-Ig or control Ig over a period of 11 d. At day 19, splenic B220+ B cells, CD4+ and CD8+ T cells, and Gr1+ and Mac-1+ populations were analyzed by flow cytometry. A representative mouse from each group is shown.
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Figure 3: Administration of BCMA-Ig reduces the peripheral B cell population. Adult Balb/c mice were treated with four intraperitoneal injections of BCMA-Ig or control Ig over a period of 11 d. At day 19, splenic B220+ B cells, CD4+ and CD8+ T cells, and Gr1+ and Mac-1+ populations were analyzed by flow cytometry. A representative mouse from each group is shown.

Mentions: Because BIAcore studies revealed that murine BAFF was able to effectively bind human BCMA-Ig, we used the fusion protein to examine the effect of disrupting the BAFF signal in normal mice. Four administrations of BCMA-Ig at intervals of 3–4 d dramatically reduced the total number of B cells in the blood and peripheral lymphoid organs examined. The B220+ B cell population in the spleen of BCMA-Ig–treated animals was reduced by 50% compared with the control Ig–treated mice. In contrast, populations of neutrophils, macrophages, CD4+ T cells, and CD8+ T cells were not significantly affected by BCMA-Ig (Fig. 3 and Table ). The decrease in absolute B cell number corresponded to the decrease in absolute total cell number (Table ), indicating that the reduction in the B cell population was not due to a concordant increase in other cell types. Therefore, the BCMA-Ig treatment specifically affected B cells. Similar results were observed in the blood and mesenteric lymph nodes, where approximately half of the B220+ B cells were lost (data not shown). As B cells do not express BAFF 25, and because human BCMA-Ig does not bind to mouse splenic B cells (data not shown), we can exclude antibody-dependent cell-mediated cytotoxicity as the mechanism of action. Although BAFF is thought to be primarily secreted, staining of splenocytes using BCMA-Ig revealed that BAFF is found on the surface of Mac-1+ cells (data not shown).


BAFF binds to the tumor necrosis factor receptor-like molecule B cell maturation antigen and is important for maintaining the peripheral B cell population.

Thompson JS, Schneider P, Kalled SL, Wang L, Lefevre EA, Cachero TG, MacKay F, Bixler SA, Zafari M, Liu ZY, Woodcock SA, Qian F, Batten M, Madry C, Richard Y, Benjamin CD, Browning JL, Tsapis A, Tschopp J, Ambrose C - J. Exp. Med. (2000)

Administration of BCMA-Ig reduces the peripheral B cell population. Adult Balb/c mice were treated with four intraperitoneal injections of BCMA-Ig or control Ig over a period of 11 d. At day 19, splenic B220+ B cells, CD4+ and CD8+ T cells, and Gr1+ and Mac-1+ populations were analyzed by flow cytometry. A representative mouse from each group is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887706&req=5

Figure 3: Administration of BCMA-Ig reduces the peripheral B cell population. Adult Balb/c mice were treated with four intraperitoneal injections of BCMA-Ig or control Ig over a period of 11 d. At day 19, splenic B220+ B cells, CD4+ and CD8+ T cells, and Gr1+ and Mac-1+ populations were analyzed by flow cytometry. A representative mouse from each group is shown.
Mentions: Because BIAcore studies revealed that murine BAFF was able to effectively bind human BCMA-Ig, we used the fusion protein to examine the effect of disrupting the BAFF signal in normal mice. Four administrations of BCMA-Ig at intervals of 3–4 d dramatically reduced the total number of B cells in the blood and peripheral lymphoid organs examined. The B220+ B cell population in the spleen of BCMA-Ig–treated animals was reduced by 50% compared with the control Ig–treated mice. In contrast, populations of neutrophils, macrophages, CD4+ T cells, and CD8+ T cells were not significantly affected by BCMA-Ig (Fig. 3 and Table ). The decrease in absolute B cell number corresponded to the decrease in absolute total cell number (Table ), indicating that the reduction in the B cell population was not due to a concordant increase in other cell types. Therefore, the BCMA-Ig treatment specifically affected B cells. Similar results were observed in the blood and mesenteric lymph nodes, where approximately half of the B220+ B cells were lost (data not shown). As B cells do not express BAFF 25, and because human BCMA-Ig does not bind to mouse splenic B cells (data not shown), we can exclude antibody-dependent cell-mediated cytotoxicity as the mechanism of action. Although BAFF is thought to be primarily secreted, staining of splenocytes using BCMA-Ig revealed that BAFF is found on the surface of Mac-1+ cells (data not shown).

Bottom Line: 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.These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Genetics, Biogen, Incorporated, Cambridge, Massachusetts 02142, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus