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Modelling Two Possible Mechanisms for the Regulation of the Germinal Center Dynamics¹

Joana S. Moreira^2,* and Jose Faro^*,

^* Estudos Avançados de Oeiras, Instituto Gulbenkian de Ciência, Oeiras, Portugal; and Departamento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Vigo, Spain

Research on the germinal center has tried to unravel the mechanisms that control its dynamics. In this study we focus on the termination of the germinal center reaction, which is still an open problem. We propose two hypothetical biological mechanisms that may be responsible for the control of germinal center dynamics and analyze them through mathematical models. The first one is based on the differentiation of follicular dendritic cells and/or T cells. Interaction of these cells in the differentiated state with germinal center B cells would promote B cell differentiation into memory B cells and Ab-forming cells, ending the germinal center reaction. The second mechanism applies only to a scenario without recycling and consists of the decay of a hypothetical proliferation signal for centroblasts that limits the number of cell divisions. Each of the models makes predictions that can be experimentally tested.

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 is supported by Fundação para Ciência e Tecnologia, Portugal, Fellowship SFRH/BD/2920/2000 (to J.M.) and Grant POCTI/36413/1999 (to J.F.). J.F. is supported by an Isidro Parga Pondal research contract with Xunta de Galicia (Santiago de Compostela, Galicia, Spain).

² Address correspondence and reprint requests to Dr. Joana S. Moreira, Estudos Avançados de Oeiras, Instituto Gulbenkian de Ciência, Apartado 14, P-2781–901 Oeiras Codex, Portugal., E-mail address: jmoreira{at}igc.gulbenkian.pt

³ Abbreviations used in this paper: GC, germinal center; AFC, Ab-forming cell; FDC, follicular dendritic cell; IC, immune complex.