Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling.
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.
Walmsley
Marita J
MJ
Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
Ooi
Steen K T
SK
Reynolds
Lucinda F
LF
Smith
Susan Harless
SH
Ruf
Sandra
S
Mathiot
Anne
A
Vanes
Lesley
L
Williams
David A
DA
Cancro
Michael P
MP
Tybulewicz
Victor L J
VL
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
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