Self-reactive B lymphocytes overexpressing Bcl-xL escape negative selection and are tolerized by clonal anergy and receptor editing.
Self-reactive B cells Tg for both a bcl-xL death inhibitory gene and an Ig receptor recognizing hen egg lysozyme (HEL-Ig) efficiently escaped developmental arrest and deletion in mice expressing membrane-bound self-antigen (mHEL). In response to the same antigen, Tg HEL-Ig B cells not expressing bcl-xL were deleted, while cells expressing bcl-2 were arrested at the immature B stage. Bcl-xL Tg B cells escaping negative selection were anergic in both in vitro and in vivo assays and showed some evidence for receptor editing. These studies suggest that Bcl-x may have a distinct role in controlling survival at the immature stage of B cell development and demonstrate that tolerance is preserved when self-reactive B cells escape central deletion.
Center for Immunology, University of Minnesota Medical School, Minneapolis 55455, USA.
W
W
Fang
B C
BC
Weintraub
B
B
Dunlap
P
P
Garside
K A
KA
Pape
M K
MK
Jenkins
C C
CC
Goodnow
D L
DL
Mueller
T W
TW
Behrens
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002678:Chimera; D017635:Clonal Anergy / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D019891:Leukopoiesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D019076:Transgenes; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C499308:Rag2 protein, mouse; D011947:Receptors, Antigen, B-Cell; C064655:V(D)J recombination activating protein 2; D051020:bcl-X Protein; C064658:RAG-1 protein