Follicular dendritic cells inhibit apoptosis in human B lymphocytes by a rapid and irreversible blockade of preexisting endonuclease

doi:10.1084/jem.181.6.1985

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Follicular dendritic cells inhibit apoptosis in human B lymphocytes by a rapid and irreversible blockade of preexisting endonuclease

E Lindhout, A Lakeman and C de Groot
Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, The Netherlands.

During germinal center reactions, a minority of B lymphocytes are selected after successful binding to follicular dendritic cells (FDCs). The majority of the B cells, however, die by apoptosis. One of the characteristics of apoptosis is rapid fragmentation of DNA by an endogenous endonuclease. The regulation of apoptosis and endonuclease activity in germinal center (GC) B cells is largely unknown. In this study we have investigated the induction and inhibition of endonuclease activity in GC B cells. We also investigated the role of FDCs, surface Ig (sIg), sIgM, CD21, CD22 CD40, and intracellular Zn2+ in the regulation of endonuclease activity. We have found that DNA fragmentation in GC B cells is caused by a preexisting endonuclease very similar to NUC-18 (an 18-kD endonuclease identified in rat thymocytes). Endonuclease activity in GC B cells appears to be rapidly and irreversibly blocked after interaction with FDCs, but not after cross-linkage of sIg, sIgM, CD21, CD22, or CD40. Addition of soluble CD40-human IgM fusion protein (sCD40) to FDC-B cell cultures also did not interfere with FDC-mediated B cell rescue. Chelation of intracellular Zn2+ during FDC-B cell cultures resulted in abrogated B cell rescue. These data suggest that FDCs inhibit apoptosis in GC B cells by a rapid inactivation of preexisting endonuclease using a mechanism distinct from CD40 ligation.
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