title: RhoA of the Rho family small GTPases is essential for B lymphocyte development.
abstract: RhoA is a member of the Rho family small GTPases that are implicated in various cell functions including proliferation and survival. However, the physiological role of RhoA in vivo remains largely unknown. Here, we deleted RhoA in the B cell and hematopoietic stem cell (HSC) populations in RhoA(flox/flox) mice with CD19 and Mx promoter-driven Cre expression, respectively. Deletion of RhoA by CD19(Cre/+) significantly blocked B cell development in spleen, leading to a marked reduction in the number of transitional, marginal zone, and follicular B cells. Surprisingly, neither B cell proliferation in response to either LPS or B cell receptor (BCR) engagement nor B cell survival rate in vivo was affected by RhoA deletion. Furthermore, RhoA(-/-) B cells, like control cells, were rescued from apoptosis by BCR crosslinking in vitro. In contrast, RhoA deficiency led to a defect in B cell activating factor (BAFF)-mediated B cell survival that was associated with a dampened expression of BAFF receptor and a loss of BAFF-mediated Akt activation. Finally, HSC deletion of RhoA by Mx-Cre severely reduced proB/preB and immature B cell populations in bone marrow while common lymphoid progenitors were increased, indicating that RhoA is also required for B cell progenitor/precursor differentiation. Taken together, our results uncover an important role for RhoA at multiple stages of B cell development.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Children's Hospital Research Foundation, Cincinnati, Ohio, United States of America.
authors.forename: Shuangmin
authors.initials: S
authors.lastname: Zhang
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhou
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lang
authors.forename: Fukun
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics; D053264:B-Cell Activating Factor / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D002470:Cell Survival; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D020741:rho GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein
chemical_list: D018941:Antigens, CD19; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D011947:Receptors, Antigen, B-Cell; C486662:Tnfrsf13c protein, mouse; C505720:Tnfsf13b protein, mouse; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein