Bcl-x rather than Bcl-2 mediates CD40-dependent centrocyte survival in the germinal center.
Both rapid B-cell proliferation and programmed cell death (PCD) occur during the differentiation and selection of B cells within the germinal center. To help elucidate the role of Bcl-x in B-cell antigen selection and PCD within the germinal center, we examined its expression in defined B-cell populations and by immunochemistry of tonsil tissue. Purified B-cell fractions enriched for centrocytes express high amounts of Bcl-x and relatively low amounts of Bcl-2, whereas fractions enriched for centroblasts lack significant levels of both proteins. Consistent with this observation, immunocytochemistry localized Bcl-x within cells scattered throughout the germinal center. Stimulation of tonsil B cells with either CD40 or Staphylococcus aureus Cowan increase bcl-x mRNA and protein levels. Treatment of a cell line with a germinal center phenotype (RAMOS) or the tonsillar B-cell centroblast fraction with CD40 rapidly increased Bcl-x levels and partially rescued B cells from PCD. These data suggest that Bcl-x rather than Bcl-2 may rescue centrocytes during selection in the germinal center.
Tuscano
J M
JM
Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA.
Druey
K M
KM
Riva
A
A
Pena
J
J
Thompson
C B
CB
Kehrl
J H
JH
D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000502:physiology*; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D018858:Germinal Center / Q000166:cytology*; D006801:Humans; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D019013:CD40 Antigens; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D051020:bcl-X Protein