oct-2 gene disruption eliminates the peritoneal B-1 lymphocyte lineage and attenuates B-2 cell maturation and function.
Targeted mutation of the gene for the Oct-2 transcription factor in mice caused neonatal lethality and abrogated mitogen-induced proliferation and differentiation of mature B lymphocytes in vitro. Here we show that Oct-2 is required for normal humoral responses upon immunization with T cell-dependent as well as T-independent Ags. oct-2-null T cell behavior was normal, implying a B cell-restricted lesion. oct-2-/- B cells displayed aberrant behavior during activation in vitro: both acquisition of markers of cellular activation and cell survival were diminished. Production of early B lineage cells in the bone marrow was normal, yet mature B cells were under-represented in blood and lymphoid organs. Furthermore, peritoneal B-1 lymphocytes were not detected in animals with a reconstituted oct-2-/- lymphoid system. We conclude that Oct-2 is required for B-1 cell maintenance and for normal Ag-driven maturation of conventional B cells in vivo.
Humbert
P O
PO
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139, USA.
Corcoran
L M
LM
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics*; D007165:Immunosuppression Therapy; D051379:Mice; D016513:Mice, SCID; D016296:Mutagenesis; D050813:Octamer Transcription Factor-2; D010537:Peritoneum / Q000166:cytology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D050813:Octamer Transcription Factor-2; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors