The role of BAFF for B cell differentiation
Final Report Abstract
The development and the survival of mature B cells is dependent on the B cell activating factor BAFF, a cytokine of the tumor necrosis superfamily. BAFF conditional knock out mice were generated to analyze the B cell stage and tissue-dependent requirements for survival signals from BAFF. C57B1/6 BAFF flox/flox cre-ER(T2) mice have normal B cell development. Only when BAFF-deficiency is induced by administration of tamoxifen, is the number of peripheral marginal zone and follicular B cells significantly reduced. When BAFF-deficiency was induced at the time point of germinal center development, we find that BAFF is required during the early phase of the germinal center reaction. In addition, we show that BAFF is required for the maintenance of memory B cells. Tissue specific BAFF deficiency revealed that the development of marginal zone B cells requires BAFF expression by FDC, myeloid cells and in addition by B cells. In contrast, the development of follicular B cells is mainly supported by BAFF expressed by follicular dendritic cells. In summary, the analysis of mice with conditional BAFF deficiency shows that expression of BAFF by myeloid cells is not sufficient for the maintenance of mature peripheral B cells. It shows that the autocrine pathway plays an important role for B cell development, in particular for that of mature marginal zone B cells.
Publications
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(2011) Eosinophils are required for the maintenance of plasma cells in the bone marrow. Nat Immunol 12(2):151-9
Chu VT, Fröhlich A, Steinhauser G, Scheel T, Roch T, Fillatreau S, Lee JJ, Löhning M, Berek C
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(2011) The long-term survival of plasma cells. Scand J Immunol. 73(6):508-11
Chu VT, Beller A, Nguyen TTN, Steinhauser G, Berek C
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(2012) Immunization induces activation of bone marrow eosinophils required for plasma cell survival. Eur J Immunol 42(1):130-7
Chu, Van T. & Berek, Claudia
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(2013) The establishment of the plasma cell survival niche in the bone marrow. Immunol Rev 251(1):177-88
Chu, Van T. & Berek, Claudia
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Plasma cell / B cell - eosinophil interactions. (2013) Chapter 11 on: Eosinophil cell-cell communication p 367 - 371. in: Eosinophils in health and disease. Editors: Lee JJ and Rosenberg HF. Elsevier
Chu VT and Berek C
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(2014) Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity. 40(4):582-93
Chu, Van Trung; Beller, Alexander; Rausch, Sebastian; Strandmark, Julia; Zänker, Michael; Arbach, Olga; Kruglov, Andrey & Berek, Claudia
