Inositol 1,4,5-trisphosphate 3-kinase B controls survival and prevents anergy in B cells.
Inositol 1,4,5-trisphosphate 3-kinase B (or Itpkb) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4), its reaction product, play an important role in the control of B lymphocyte fate and function in vivo. In order to investigate the fine mechanisms of Itpkb and Ins(1,3,4,5)P4 action in B cells, we crossed Itpkb(-/-) mice with transgenic mice expressing a 3-83μδ B cell receptor (BCR) specific for membrane-bound MHC-I H2-K(b) and H2-K(k) molecules. On a non-deleting H2-K(d) genetic background, we show that Itpkb is important for the control of Bim protein expression and B cell survival rather than for the control of B cell development from one stage to another. Analyses of cell surface markers expression, proapoptotic Bim protein expression, in vitro survival and in vivo turnover demonstrated that BCR transgenic Itpkb(-/-) B cells exhibit an anergic phenotype with the notable exception of their enhanced antigen-induced calcium signalling. On a deleting H2-K(b) genetic background, we show that Itpkb is not essential for BCR editing or negative selection. These data establish Itpkb as an important regulator of B cell survival and anergy in vivo.
Maréchal
Yoann
Y
Institut de Recherches Interdisciplinaires en Biologie Humaine et Moléculaire (IRIBHM), Institut de Biologie et de Médecine Moléculaires (IBMM), Faculté de Médecine, Université Libre de Bruxelles, Gosselies, Belgium. ymarecha@ulb.ac.be
Quéant
Séverine
S
Polizzi
Selena
S
Pouillon
Valérie
V
Schurmans
Stéphane
S
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D020013:Calcium Signaling / Q000235:genetics; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D006183:H-2 Antigens / Q000276:immunology; D007295:Inositol Phosphates / Q000276:immunology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007295:Inositol Phosphates; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; C081655:inositol-1,3,4,5-tetrakisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C051038:Inositol 1,4,5-trisphosphate 3-kinase