Association of SWAP-70 with the B cell antigen receptor complex

Masat, Linda; Caldwell, J. D.; Armstrong, Richard J. E.; Khoshnevisan, H.; Jessberger, Rolf; Herndier, Brian; Wabl, Matthias; Ferrick, David A.

doi:10.1073/pnas.040374497

Cited by 51 publications

(50 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Retrovirus was produced by cotransfecting ecotropic packaging plasmids and SWAP-70-IRES-GFP or IRES-GFP retrovirus vectors that have been described previously (29) into 293T cells using Polyethyleneimine (Sigma). Virus was harvested 48 hours after transfection.…”

Section: Retroviral Transductionmentioning

confidence: 99%

Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70

Garbe

Roscher

Schüler

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Bone remodeling involves tightly regulated bone-resorbing osteoclasts and bone-forming osteoblasts. Determining osteoclast function is central to understanding bone diseases such as osteoporosis and osteopetrosis. Here, we report a novel function of the F-actin binding and regulatory protein SWAP-70 in osteoclast biology. F-actin ring formation, cell morphology, and bone resorption are impaired in

show abstract

Section: Retroviral Transductionmentioning

confidence: 99%

Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70

Garbe

Roscher

Schüler

et al. 2012

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…33,35,36 The presence of NLS and NES suggests that SWAP-70 may shuttle between the cytoplasm and the nucleus, an assumption that we showed to be correct. 34 The PH domain of SWAP-70 specifically binds phosphatidylinositol 3,4,5-triphosphate (PIP3). In addition, SWAP-70 binds nonmuscle Factin.…”

Section: Introductionmentioning

confidence: 99%

“…33,34 The protein contains a coiled-coil region, a pleckstrin homology (PH) domain, 3 nuclear localization signals (NLSs), a nuclear exit signal (NES), a domain weakly homologous to Dbl (DH) domains, and a putative EF-hand. 33,35,36 The presence of NLS and NES suggests that SWAP-70 may shuttle between the cytoplasm and the nucleus, an assumption that we showed to be correct.…”

Section: Introductionmentioning

confidence: 99%

SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation

Quéméneur

Angeli

Chopin

et al. 2008

Blood

View full text Add to dashboard Cite

IntroductionB lymphocytes are central to efficient innate and adaptive immune responses. In innate immunity, B cells such as those forming the marginal zone surrounding the follicles in the spleen respond rapidly to T-independent compounds such as bacterial lipopolysaccharides. [1][2][3] In adaptive immunity, B cells in the spleen or the lymph node (LN) follicles are stimulated through direct contact with T cells, perform Ig class switching and somatic hypermutation, and then as plasma cells produce high-affinity antibodies. 4 Memory cells develop for later revitalization of a specific immune response. [5][6][7] After immunization with a T-dependent antigen, an oligoclonal cohort of B cells is activated along the border of the T-cell areas of secondary lymphoid organs. 8,9 Following interaction with T cells, activated B cells migrate either to extrafollicular foci or to B follicles. 10,11 B cells that emigrate to extrafollicular foci within the red pulp of the spleen differentiate into short-lived Ab-secreting cells producing low-affinity Ig. 12 Approximately 1 week after initial immunization, some antigen-primed B cells migrate back to the follicles and together with follicular B cells form germinal centers (GCs). [13][14][15][16] GCs are inducible lymphoid microenvironments composed primarily of antigen-specific B cells, antigen-specific CD4 ϩ follicular T cells, 17 and follicular dendritic cells (FDCs). 18,19 GCs are sites of rapid antigen-specific B-cell selection and expansion, affinity maturation by somatic hypermutation, isotype switching, and receptor editing, and are sites of apoptosis of B cells, which fail in selection. 15,16,[20][21][22] The GC reaction generates long-lived plasma cells and memory B cells. 7,13,23 GCs can be detected in situ and by fluorescence-activated cell sorting (FACS) by staining for peanut agglutinin (PNA) or with anti-GL7. 24 The GC can be subdivided into the light zone enriched in noncycling B cells (centrocytes) and the dark zone containing more proliferating B cells (centroblasts). The zones can be further distinguished by staining for FDCs and stroma expressing CXCL13 besides CXCR5 high B cells in the light zone, and CXCR4 high centroblasts and CXCL12 ϩ stroma in the dark zone. 25 This separation into light and dark zones and their functions may not be as strict as hitherto assumed, since recent reports have shed light on GC B-cell dynamics and showed that GC B cells exhibit polarized shape, are very motile, and transit between dark and light zones. [26][27][28][29][30] Migration is therefore an important parameter for GC functions and much remains to be elucidated about GC induction and the mechanisms that control the commitment to either extrafollicular reaction or GC formation.A number of molecules involved in the transduction of signals from cell-surface receptors to adhesion molecules and to the F-actin cytoskeleton regulate migration, cell adhesion, and transmigration into the tissues. Notably, small G-proteins of the Rho family (eg, Rac-1, Rac-2), together with the...

show abstract

“…21 Although its regulation of Rac and actin polymerization are likely to be important for SWAP-70's function in regulating B-cell migration, little is known about how SWAP-70 itself is regulated, other than its interaction with PIP 3 , which is required for its localization. 22 Therefore, we asked whether and how SWAP-70 is posttranslationally modified, and, if phosphorylated, which kinase might be responsible. Upon identifying SYK as a kinase that phosphorylates SWAP-70, the requirement for SYK in regulating B-cell migration was determined.…”

mentioning

confidence: 99%

SYK regulates B-cell migration by phosphorylation of the F-actin interacting protein SWAP-70

Pearce

Audzevich

Jessberger

2011

Blood

View full text Add to dashboard Cite

IntroductionMigration of B cells into secondary lymphoid organs is required for an antigen-specific humoral immune response. B cells migrate from the bloodstream to lymph nodes by extravasation from high endothelial venules. The response to chemokines and integrinmediated adhesion to endothelial cells is a key step in this process. 1 B cells in secondary lymphoid organs are critical to homeostatic and inflammatory regulation of these tissues. If the lymph node becomes inflamed, B-cell migration is a prerequisite for normal hypertrophy and the further recruitment of dendritic and T cells. 2 B-cell trafficking within lymph nodes is also important during the generation of the germinal center reaction and humoral immune responses. [3][4][5][6] Abnormal chemoattractant-mediated B-cell migration is central to infiltration of malignant B cells into tissues and formation of ectopic germinal centers in autoimmune diseases. [7][8][9] The transduction of signals from cell surface receptors to the actin cytoskeleton to regulate cell adhesion and migration requires small G proteins of the Ras superfamily. [10][11][12] These include members of the Ras family, including Ras and Rap1, and members of the Rho family, such as Rac, Cdc42, and Rho. 13 Upstream activators of Rho proteins such as the Dbl homology domain proteins of the Vav family are required for ␤-integrin and chemokine-mediated Rac, Cdc42, and Rho activation and stable adhesions of cells. 14 Although B-cell migration is vital for their development, the pathways underlying integrin and chemokine signals in B cells are poorly defined. We identified the signaling protein SWAP-70 15 as required for B-cell migration and adhesion in vitro and in vivo. 16 Swap70 Ϫ/Ϫ B cells show aberrant integrin-mediated adhesion, defective polarization, and do not form uropods and stabilized lamellipodia in vitro. This leads to a defect in migration and homing of B cells to lymph nodes in vivo. In correlation with these defects in migration and adhesion, Swap70 Ϫ/Ϫ transitional B cells hyperadhere to the splenic red pulp and are impaired in differentiation into marginal zone B-cells. 17 In addition, Swap70 Ϫ/Ϫ B cells do not generate a normal germinal center response, 18 a process requiring high B-cell motility and a dynamic morphology, 6 which are most likely disturbed by the absence of SWAP-70.SWAP-70 interacts with and regulates proteins of the Rho family, in particular Rac and RhoA. 19,20 Unusually, SWAP-70 has a Dbl homology domain to the C-terminus of its pleckstrin homology (PH) domain. 20 The PH domain binds PIP 3 and SWAP-70 also binds F-but not G-actin. 20,21 The binding of SWAP-70 to F-actin depends on cell stimulation and is required for regulation of cytoskeletal rearrangements such as membrane ruffles. 21 Although its regulation of Rac and actin polymerization are likely to be important for SWAP-70's function in regulating B-cell migration, little is known about how SWAP-70 itself is regulated, other than its interaction with PIP 3 , which is required for its localization. ...

show abstract

Association of SWAP-70 with the B cell antigen receptor complex

Cited by 51 publications

References 19 publications

Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70

Regulation of bone mass and osteoclast function depend on the F-actin modulator SWAP-70

SWAP-70 deficiency causes high-affinity plasma cell generation despite impaired germinal center formation

SYK regulates B-cell migration by phosphorylation of the F-actin interacting protein SWAP-70

Contact Info

Product

Resources

About