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In Vitro and In Vivo Activation Induces BAFF and APRIL Expression in B Cells¹

Van Trung Chu^*, Philipp Enghard, Gabriela Riemekasten and Claudia Berek^2,*

^* Deutsches Rheuma ForschungsZentrum; and Department of Rheumatology and Clinical Immunology, Charite University Hospital, Berlin, Germany

B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) play key roles in peripheral B cell survival, maturation, and differentiation. BAFF and APRIL are produced by a variety of cell types such as macrophages/monocytes and dendritic cells. Our analysis shows that BAFF mRNA is also expressed in all B cell subsets isolated from bone marrow, spleen, and peritoneal cavity of BALB/c mice. APRIL expression is restricted to early stages of B cell development in the bone marrow and the peritoneal B1 subset. Stimulation of B2 and B1 cells with LPS or CpG-oligodeoxynucleotides induced MyD88-dependent plasma cell differentiation and intracellular expression of BAFF and APRIL. Furthermore, activation of B cells up-regulated membrane expression of BAFF. The finding that in vitro activation of B cells is inhibited by the antagonist transmembrane activator and calcium modulator ligand interactor Ig, indicates that BAFF and/or APRIL are released into the culture supernatants. It shows that B cell survival, proliferation, and differentiation are supported by an autocrine pathway. In vivo activation of B cells with a T-dependent Ag- induced BAFF expression in germinal center B cells. In (NZB x NZW)F₁ mice with established autoimmune disease, marginal zone, germinal center B cells, as well as splenic plasma cells expressed high levels of BAFF. In (NZB x NZW)F₁ mice, the continuous activation of B cells and thus overexpression of BAFF and APRIL may contribute to the development of autoimmune disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by a grant from the Government of Vietnam and the DAAD (to V.T.C.), the Bundesministerium für Bildung und Forschung Grant NGFN2 and the SFB 650. The DRFZ is supported by the Berlin Senate of Research and Education.

² Address correspondence and reprint requests to Dr. Claudia Berek, Deutsches Rheuma ForschungsZentrum, Chariteplatz 1, Berlin, Germany. E-mail address: berek{at}drfz.de

³ Abbreviations used in this paper: BAFF, B cell-activating factor; APRIL, a proliferation-inducing ligand; MZ, marginal zone; FO, follicular; GC, germinal center; FDC, follicular dendritic cells; CMK, chloromethylketone; phOx, 2-phenyl-oxazolone; PNA, peanut agglutinin; MFI, mean fluorescence intensity; TACI, transmembrane activator and calcium modulator ligand interactor; ODN, oligodeoxynucleotide; BAFF-R, BAFF receptor.

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