Abstract
Lymphocyte survival during immune responses is controlled by the relative expression of pro- and anti-apoptotic molecules, regulating the magnitude, quality, and duration of the response. We investigated the consequences of deleting genes encoding the anti-apoptotic molecules Mcl1 and Bcl2l1 (Bcl-x(L)) from B cells using an inducible system synchronized with expression of activation-induced cytidine deaminase (Aicda) after immunization. This revealed Mcl1 and not Bcl2l1 to be indispensable for the formation and persistence of germinal centers (GCs). Limiting Mcl1 expression reduced the magnitude of the GC response with an equivalent, but not greater, effect on memory B cell formation and no effect on persistence. Our results identify Mcl1 as the main anti-apoptotic regulator of activated B cell survival and suggest distinct mechanisms controlling survival of GC and memory B cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibody Affinity
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B-Lymphocytes / immunology*
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Cell Survival
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Gene Deletion
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Germinal Center / cytology
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Germinal Center / immunology*
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Immunologic Memory*
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / immunology*
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bcl-X Protein / genetics
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bcl-X Protein / immunology
Substances
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Mcl1 protein, mouse
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins c-bcl-2
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bcl-X Protein
Associated data
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GENBANK/HM804028
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GENBANK/HM804029
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GENBANK/HM804030
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GENBANK/HM804031
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GENBANK/HM804032
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GENBANK/HM804033
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GENBANK/HM804034
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GENBANK/HM804035
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GENBANK/HM804036
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GENBANK/HM804037
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GENBANK/HM804038
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GENBANK/HM804039
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GENBANK/HM804040
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GENBANK/HM804041
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GENBANK/HM804042
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GENBANK/HM804043
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GENBANK/HM804044
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GENBANK/HM804045
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GENBANK/HM804046
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GENBANK/HM804047
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GENBANK/HM804048
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GENBANK/HM804049
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GENBANK/HM804050
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GENBANK/HM804051
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GENBANK/HM804052
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GENBANK/HM804053
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GENBANK/HM804054
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GENBANK/HM804055
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GENBANK/HM804056
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GENBANK/HM804057
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GENBANK/HM804058
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GENBANK/HM804059
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GENBANK/HM804060
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GENBANK/HM804061
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GENBANK/HM804062
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GENBANK/HM804063
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GENBANK/HM804064
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GENBANK/HM804065
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GENBANK/HM804066
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GENBANK/HM804067
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GENBANK/HM804068
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GENBANK/HM804069
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GENBANK/HM804070
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GENBANK/HM804071
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GENBANK/HM804072
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GENBANK/HM804073
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GENBANK/HM804074
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GENBANK/HM804075
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GENBANK/HM804076
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GENBANK/HM804077
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GENBANK/HM804078
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GENBANK/HM804079
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GENBANK/HM804080
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GENBANK/HM804081
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GENBANK/HM804082
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GENBANK/HM804083
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GENBANK/HM804084