A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation.
Mice lacking the p110delta catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II thymus-independent antigen, and are defective in their primary and secondary responses to thymus-dependent antigen. p110delta(-/-) B cells proliferate poorly in response to B cell receptor (BCR) or CD40 signals in vitro, fail to activate protein kinase B, and are prone to apoptosis. p110delta function is required for BCR-mediated calcium flux, activation of phosphlipaseCgamma2, and Bruton's tyrosine kinase. Thus, p110delta plays a critical role in B cell homeostasis and function.
Clayton
Elizabeth
E
Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom.
Bardi
Giuseppe
G
Bell
Sarah E
SE
Chantry
David
D
Downes
C Peter
CP
Gray
Alexander
A
Humphries
Lisa A
LA
Rawlings
David
D
Reynolds
Helen
H
Vigorito
Elena
E
Turner
Martin
M
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D007527:Isoenzymes / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis; D051966:Phospholipase C gamma; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology
D000077329:Agammaglobulinaemia Tyrosine Kinase; D002118:Calcium; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D051966:Phospholipase C gamma; D017346:Protein Serine-Threonine Kinases; D021122:Protein Subunits; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011947:Receptors, Antigen, B-Cell; D010738:Type C Phospholipases; C060974:phosphatidylinositol 3,4,5-triphosphate; C000625951:Btk protein, mouse