Follicular dendritic cells inhibit apoptosis in human B lymphocytes by a rapid and irreversible blockade of preexisting endonuclease.
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.
Lindhout
E
E
Academic Medical Center, University of Amsterdam, Department of Cell Biology and Histology, The Netherlands.
Lakeman
A
A
de Groot
C
C
D015703:Antigens, CD / Q000032:analysis; D017209:Apoptosis / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002450:Cell Communication; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004720:Endonucleases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D014066:Palatine Tonsil / Q000276:immunology
D015703:Antigens, CD; D004720:Endonucleases