title: Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling.
abstract: The Rac1 guanosine triphosphatase (GTPase) has been implicated in multiple cellular functions, including actin dynamics, proliferation, apoptosis, adhesion, and migration resulting from signaling by multiple receptors, including the B cell antigen receptor (BCR). We used conditional gene targeting to generate mice with specific Rac1 deficiency in the B cell lineage. In the absence of both Rac1 and the highly related Rac2, B cell development was almost completely blocked. Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance.
authors.affiliation: Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
authors.forename: Marita J
authors.initials: MJ
authors.lastname: Walmsley
authors.forename: Steen K T
authors.initials: SK
authors.lastname: Ooi
authors.forename: Lucinda F
authors.initials: LF
authors.lastname: Reynolds
authors.forename: Susan Harless
authors.initials: SH
authors.lastname: Smith
authors.forename: Sandra
authors.initials: S
authors.lastname: Ruf
authors.forename: Anne
authors.initials: A
authors.lastname: Mathiot
authors.forename: Lesley
authors.initials: L
authors.lastname: Vanes
authors.forename: David A
authors.initials: DA
authors.lastname: Williams
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
authors.forename: Victor L J
authors.initials: VL
authors.lastname: Tybulewicz
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D016175:B-Lymphocyte Subsets / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002470:Cell Survival; D005260:Female; D018390:Gene Targeting; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein / Q000502:physiology*; D000097766:RAC2 GTP-Binding Protein
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D008565:Membrane Proteins; D011947:Receptors, Antigen, B-Cell; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000097766:RAC2 GTP-Binding Protein; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse