Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis.
B cells undergo selection within germinal centers on the basis of their capacity to be activated by antigen held on follicular dendritic cells. Isolated germinal center B cells in culture kill themselves by apoptosis but this is prevented if their receptors for antigen are cross-linked. In this study it is confirmed that almost all germinal center B cells, unlike other B cells, do not express the 25-kDa protein encoded by the bcl-2 oncogene. Cross-linking the surface Ig of isolated germinal center cells causes them to express bcl-2 protein. Two other stimuli which inhibit the entry of germinal center cells to apoptosis result in the expression of bcl-2 protein. These stimuli are: (a) CD40 antibody and (b) recombinant 25-kDa fragment of the CD23 protein plus recombinant interleukin 1 alpha. Respectively, these induce germinal center cells to differentiate to resting B cells or plasmablasts. Dual-fluorescence studies on small lymphocytes confirm the presence of bcl-2 protein in mitochondria but show that this is also present in other extra-nuclear areas. Burkitt lymphoma cells have a phenotype which indicates that they are neoplastic cells of germinal center origin. The expression of bcl-2 protein by Burkitt lymphoma lines was also studied. Burkitt lines which retain the phenotype of fresh Burkitt lymphoma cells can be induced to enter apoptosis on culture with the Ca2+ ionophore ionomycin. These cells were found not to express bcl-2 protein. By contrast, Burkitt lines which have drifted towards a lymphoblastoid cell line phenotype and are resistant to the induction of apoptosis express high levels of the bcl-2 protein. The findings support the concept that the susceptibility of germinal center cells to entering apoptosis is associated with their lack of expression of bcl-2 protein. Aberrant expression of bcl-2 protein by some neoplastic germinal center cells may allow survival in situations where their normal counterparts die.
Liu
Y J
YJ
Department of Immunology, University of Birmingham Medical School, Great Britain.
Mason
D Y
DY
Johnson
G D
GD
Abbot
S
S
Gregory
C D
CD
Hardie
D L
DL
Gordon
J
J
MacLennan
I C
IC
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000737:chemistry*; D002051:Burkitt Lymphoma / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D008928:Mitochondria / Q000737:chemistry; D011518:Proto-Oncogene Proteins / Q000032:analysis* / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2
D000911:Antibodies, Monoclonal; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2