A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development.
B-cell development is orchestrated by complex signaling networks. Rap1 is a member of the Ras superfamily of small GTP-binding proteins and has 2 isoforms, Rap1a and Rap1b. Although Rap1 has been suggested to have an important role in a variety of cellular processes, no direct evidence demonstrates a role for Rap1 in B-cell biology. In this study, we found that Rap1b was the dominant isoform of Rap1 in B cells. We discovered that Rap1b deficiency in mice barely affected early development of B cells but markedly reduced marginal zone (MZ) B cells in the spleen and mature B cells in peripheral and mucosal lymph nodes. Rap1b-deficient B cells displayed normal survival and proliferation in vivo and in vitro. However, Rap1b-deficient B cells had impaired adhesion and reduced chemotaxis in vitro, and lessened homing to lymph nodes in vivo. Furthermore, we found that Rap1b deficiency had no marked effect on LPS-, BCR-, or SDF-1-induced activation of mitogen-activated protein kinases and AKT but clearly impaired SDF-1-mediated activation of Pyk-2, a key regulator of SDF-1-mediated B-cell migration. Thus, we have discovered a critical and distinct role of Rap1b in mature B-cell trafficking and development of MZ B cells.
Chen
Yuhong
Y
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
Yu
Mei
M
Podd
Andrew
A
Wen
Renren
R
Chrzanowska-Wodnicka
Magdalena
M
White
Gilbert C
GC
Wang
Demin
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D020668:rap GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D020827:rap1 GTP-Binding Proteins / Q000172:deficiency / Q000502:physiology*
D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D051418:Focal Adhesion Kinase 2; C496053:Ptk2b protein, mouse; C492136:Rap1b protein, mouse; D020668:rap GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins