ライフサイエンスコーパス: BLyS

1 BLyS (BAFF), a cytokine essential for mature B cell deve

2 BLyS and its major receptor BAFF-R have been shown to be

3 BLyS binds to 3 TNF-R receptors, TACI, BCMA, BAFF-R, to

4 BLyS blockade has little effect on IgG levels in normal

5 BLyS blocks the cell volume loss (atrophy) that freshly

6 BLyS expression was studied in neutrophils from the syno

7 BLyS family ligands and receptors are key players in the

8 BLyS is involved in regulation of B-cell activation and

9 BLyS levels affect survival signals and selective apopto

10 BLyS levels are associated with multiple forms of humora

11 BLyS levels were uniquely correlated among IPF patients

12 BLyS receptors are expressed only on B cells and not pre

13 BLyS responsiveness thus balances peripheral selection a

14 BLyS stimulation activates 2 independent signaling pathw

15 BLyS was present in similar levels in all tissue types a

16 BLyS(high) peptide-pulsed bone marrow-derived DCs, used

17 BLyS-DCs secreted elevated levels of the major Th1-polar

18 BLyS-dependent survival requires the antiapoptotic prote

19 BLyS-stimulated DCs (BLyS-DCs) were also able to augment

20 gation with BAFF ligand (also called TALL-1, BLyS, THANK, or zTNF4).

21 s, SELENA-SLEDAI 3.3 (median 2, range 0-18), BLyS 5.57 ng/ml, IgG 1,439 mg/dl, C3 104.4 mg/dl, and C4

22 enrolled in a clinical trial of belimumab, a BLyS-specific inhibitor, plus standard of care therapy w

23 apid release of soluble, biologically active BLyS/BAFF from myeloid cells.

24 After BLyS neutralization, indefinite islet allograft survival

25 ed in EAE marmosets treated with mAb against BLyS or APRIL, where B cell depletion via withdrawal of

26 s study, we show that TLR stimuli also alter BLyS receptor expression, but in contrast to BCR ligatio

27 Although BLyS costimulates adaptive immune cells, the ability of

28 However, although BLyS enhances viability among TLR stimulated B cells, AP

29 Despite ample BLyS retention on B cells in follicular (FO) regions, th

30 es to influenza vaccination (P = 0.863), and BLyS levels increased postvaccination only in the subset

31 ovium-SCID mouse chimeras with the APRIL and BLyS decoy receptor transmembrane activator and CAML int

32 Moreover, APRIL and BLyS have been identified as potential therapeutic targe

33 In contrast, inhibition of APRIL and BLyS in aggregate and diffuse synovitis left Ig levels u

34 Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS

35 ealthy controls, the expression of APRIL and BLyS mRNA and protein was upregulated in natural and exp

36 Moreover, APRIL and BLyS partially colocalized with kappa L chain-expressing

37 s both the B cell antigen receptor (BCR) and BLyS receptor 3 (BR3), which suggests that these recepto

38 R, that resulted in reduced BLyS binding and BLyS-mediated survival.

39 Abnormalities of B cells and BLyS are common in IPF patients, and highly associated w

40 te stimulator (BLyS) receptor expression and BLyS binding capacity, these cells do not rely on BLyS f

41 the constitutive activation of NF-kappaB and BLyS in NHL-B cells forms a positive feedback loop assoc

42 and despite successful therapy in plasma and BLyS-overexpressing blood mDCs of HIV-infected rapid and

43 peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secre

44 Belimumab, a human neutralizing anti-BLyS monoclonal antibody, has delivered moderate but pos

45 APRIL production and for expression of APRIL/BLyS receptors.

46 lls and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be sep

47 necrosis factor family (BAFF; also known as BLyS) is a cytokine that enhances B-cell survival and pr

48 BAFF (also known as BLyS), a member of the tumor necrosis factor superfamily

49 ctor of the TNF family ((BAFF) also known as BLyS, TALL-1, zTNF-4, THANK, and TNSF13B), a B cell grow

50 The interaction of BAFF, also known as BLyS, with its receptors BAFFR and TACI on B cells is cr

51 calls for circumspection prior to assigning BLyS as a candidate therapeutic target in this disorder.

52 The TNF-family cytokine BAFF (BLyS) promotes B lymphocyte survival and is overexpresse

53 ast decade, insights into the roles of BAFF (BLyS) and APRIL in lymphoma development have helped to u

54 g factor belonging to the TNF family (BAFF) (BLyS) plays a fundamental role in regulating peripheral

55 he regulator B cell-activating factor (BAFF, BLyS), a TNF family protein with powerful immunoregulato

56 ecifically and exclusively to IL-21 and BAFF/BLyS by differentiating into IgG-secreting PC, and thus

57 ing factor belonging to the TNF family (BAFF/BLyS) that synergize in the absence of further costimula

58 ignificant increases in serum levels of BAFF/BLyS and by increases in BAFF-producing Ly6C(hi) inflamm

59 The TNF family member protein BAFF/BLyS is essential for B cell survival and plays an impor

60 Baseline BLyS levels in patients were not correlated with humoral

61 s, and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after

62 vaccination is not correlated with baseline BLyS levels in SLE patients, and only those patients wit

63 Finally, we find that both BLyS and APRIL enhance viability among quiescent and BCR

64 B cells are readily protected from death by BLyS stimulation, but this protection is completely abro

65 Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this alpha-apoptotic gene product may

66 Antagonistic cell-cycle regulation by BLyS and p18(INK4c) is functionally linked to apoptotic

67 factor of the TNF family (BAFF; also called BLyS).

68 promoters of NF-kappaB target genes, CD154, BLyS/BAFF, and Bfl-1/A1, in various LBCL cell lines.

69 monstrate a relationship between circulating BLyS levels and SLE disease activity.

70 ch Fcgamma receptors can elevate circulating BLyS levels and promote autoantibody production in immun

71 BLyS-stimulated DCs (BLyS-DCs) were also able to augment allogeneic CD4 T cel

72 Whereas T cell-derived BLyS is dispensable for normal GC cellularity and somati

73 on, high affinity clones rely on TFH-derived BLyS for their persistence.

74 Elevated BLyS levels were also associated with anti-nuclear RNP (

75 Elevated BLyS levels were associated with increased disease activ

76 he subsequent visit, and between an elevated BLyS level at the previous visit and a greater SELENA-SL

77 rty percent of the SLE patients had elevated BLyS levels, with African American patients having highe

78 vity was a significant predictor of elevated BLyS in a multivariate analysis (P = 0.002).

79 tients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 i

80 We found that elevated BLyS levels were more common in patients with familial B

81 disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of

82 Additionally, excess BLyS does not rescue HKI B cells from selective eliminat

83 Intriguingly, provision of excess BLyS prior to immunization led to a consistent improveme

84 ated monocytes bound low levels of exogenous BLyS and expressed primarily intracellular TACI, and cel

85 mine the sensitivity of B cells to exogenous BLyS.

86 e patients were less responsive to exogenous BLyS.

87 a B-cell disease and CLL lymphocytes express BLyS receptors.

88 inflammation, they release surface-expressed BLyS in a TNFalpha-dependent manner, and thus may contri

89 responsiveness to the B cell survival factor BLyS (also termed BAFF), decreased expression of the BLy

90 Plasma B lymphocyte stimulating factor (BLyS) was assayed by ELISA.

91 ctivating factor belonging to the TNF family/BLyS survival factor, integrin-regulated homeostasis, an

92 In contrast, use of AdTACI for BLyS blockade had only transient effects on the levels o

93 GC B cells, thus limiting their capacity for BLyS binding and retention.

94 competition with non-autoreactive cells for BLyS, but remain at a competitive disadvantage for other

95 known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of expression was variable.

96 lin ligand interactor (TACI), a receptor for BLyS and APRIL, mounted an initial antiviral B cell resp

97 Total available receptors for BLyS were decreased in patients with SLE, independent of

98 Total available receptors for BLyS were measured by analysis of binding of recombinant

99 enced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survi

100 d we therefore sought to identify a role for BLyS and its receptors in non-Hodgkin lymphoma (NHL).

101 to assess whether there is a direct role for BLyS in modulating human DC functions.

102 A role for BLyS in the survival of malignant B cells has also been

103 inical immunotherapeutic agents specific for BLyS, and its family of cytokines, has emerged for the t

104 es representing the 3 types of synovitis for BLyS and APRIL production and for expression of APRIL/BL

105 Sera were tested for BLyS levels, lupus-associated autoantibodies, serum inte

106 Independent of its survival function, BLyS enhances the synthesis of cyclin D2, in part throug

107 The 25% of IPF subjects with the greatest BLyS values also had diminished 1-y survival (46 +/- 11%

108 s with de novo large B-cell lymphoma, a high BLyS level correlated with a poorer median overall survi

109 Nef thus contributes to high BLyS proinflammatory profiles in HIV-infected individual

110 this study may explain more clearly why high BLyS production is often correlated with certain inflamm

111 rican American patients with SLE have higher BLyS levels regardless of disease activity.

112 with African American patients having higher BLyS levels than white patients (P = 0.006).

113 he previous visit was associated with higher BLyS levels at the previous visit (P = 0.0042) and with

114 rs, TACI and BCMA, with another TNF homolog, BLyS/BAFF.

115 mbrane and in intracellular stores; however, BLyS release from each of these sites was found to be re

116 than do splenic FO or peritoneal B2 cells in BLyS/LPS/TGF-beta.

117 cells, especially marginal zone B cells, in BLyS-treated mice.

118 nd to NF-kappaB targeted promoters including BLyS, CD154, Bcl-xL, IL-8, and Bfl-1/A1, promoting the t

119 aseline BLyS levels demonstrate an increased BLyS response after vaccination.

120 city in mature B cells, reflecting increased BLyS receptor levels.

121 ysregulations were associated with increased BLyS expression in plasma and by blood myeloid DCs (mDCs

122 Recent evidence indicates BLyS receptor levels shift following BCR ligation, sugge

123 used to define expression of the individual BLyS receptors on subsets of B cells in blood, spleen, a

124 cgammaRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation.

125 ranulocyte colony-stimulating factor induced BLyS release from the intracellular stores.

126 nt assay and for blood leukocyte full-length BLyS and DeltaBLyS messenger RNA (mRNA) levels by quanti

127 46 +/- 11%), compared with those with lesser BLyS concentrations (81 +/- 5%) (hazard ratio = 4.0, 95%

128 SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels are elevated in pediatric SLE.

129 s were normal in JIA despite blood leukocyte BLyS mRNA levels being elevated to degrees similar to th

130 SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels were each significantly elevated, and p

131 BLyS protein levels, but not blood leukocyte BLyS mRNA levels, were correlated with disease activity.

132 rmal in JIA despite elevated blood leukocyte BLyS mRNA levels.

133 esponding patients had a significantly lower BLyS level than those with progressive disease.

134 Among JIA patients, neither BLyS parameter was correlated with disease activity.

135 APRIL does not, suggesting that TACI but not BLyS receptor 3 may share survival promoting pathways wi

136 ulates adaptive immune cells, the ability of BLyS to stimulate innate immune cells has not been descr

137 gregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor si

138 require overcoming the persistent binding of BLyS to BAFF-R.

139 Blockade of BLyS ameliorates B cell-dependent disease manifestations

140 Blockade of BLyS, via transmembrane activator and cyclophilin ligand

141 Plasma concentrations of BLyS, an obligate factor for B cell survival and differe

142 This study examined the effect of BLyS blockade in 3 animal models of lupus.

143 Biologic effects of BLyS and APRIL were explored by treating human synovium-

144 s for understanding the potential effects of BLyS blockade in human disease.

145 undertaken to investigate the expression of BLyS and regulation of BLyS release from the surface of

146 Expression of BLyS was detected on the surface of peripheral blood neu

147 Constitutive expression of BLyS was observed in neutrophils, both on the cell membr

148 fluid were study for membrane expression of BLyS.

149 The failure of BLyS to induce S-phase cell-cycle entry lies in its inab

150 While the soluble form of BLyS/BAFF is thought to be the primary biologically acti

151 t studies have underscored the importance of BLyS and APRIL as factors that can support the survival

152 High levels of BLyS may relax B cell selection and contribute to autoan

153 mined by flow cytometry, and serum levels of BLyS, IgM, IgA, and IgG rheumatoid factors (RFs), anti-c

154 s to study the mechanisms of surface loss of BLyS.

155 This review discusses the mechanism of BLyS action on B cells, its role in SLE, and specific ta

156 ate the expression of BLyS and regulation of BLyS release from the surface of neutrophils infiltratin

157 stimuli, only TNFalpha triggered release of BLyS from the neutrophil membrane.

158 The fundamental role of BLyS in transitional B cell selection, coupled with the

159 fluid led to TNFalpha-dependent shedding of BLyS from the cell surface.

160 cells (TFH cells) provide a local source of BLyS.

161 , its role in SLE, and specific targeting of BLyS in the treatment of SLE.

162 e suggest that an increased understanding of BLyS-regulated processes may help the design of vaccine

163 udy, we demonstrate the potential utility of BLyS-directed immunotherapy in preventing allograft reje

164 rm the dependence of newly formed B cells on BLyS for survival in humans.

165 due to a higher dependency of HKI B cells on BLyS for survival.

166 higher dependency of autoreactive B cells on BLyS.

167 binding capacity, these cells do not rely on BLyS for survival.

168 Thus, we hypothesized that APRIL and/or BLyS are upregulated in periodontitis and contribute to

169 Ab-mediated neutralization of APRIL or BLyS diminished the number of B cells in the gingival ti

170 B cells with anti-CD40 mAb, LPS, CpG DNA, or BLyS has previously been shown to induce activation of N

171 sculitic involvement, elevated anti-dsDNA or BLyS levels, or low C3 had increased risk of clinically

172 sting that activation cues can alter overall BLyS receptor profiles and thus ligand sensitivity.

173 double-stranded DNA (anti-dsDNA), and plasma BLyS levels.

174 were each significantly elevated, and plasma BLyS protein levels, but not blood leukocyte BLyS mRNA l

175 in adults with rheumatoid arthritis, plasma BLyS protein levels are normal in JIA despite elevated b

176 In contrast, plasma BLyS protein levels were normal in JIA despite blood leu

177 a 6-month interval were analyzed for plasma BLyS protein levels by enzyme-linked immunosorbent assay

178 The correlation of plasma BLyS protein levels with disease activity points to BLyS

179 at, as previously noted in adult SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels are el

180 In pediatric SLE, plasma BLyS protein and blood leukocyte BLyS mRNA levels were e

181 Univariate analysis showed that plasma BLyS levels were associated with anti-dsDNA titers (P =

182 duction in the expression of the more potent BLyS receptor, BAFF-R, that resulted in reduced BLyS bin

183 ch produce IgM, and macrophages that produce BLyS/BAFF/TNFSF13B, a member of the TNF superfamily impl

184 rmalization of serologic activity and reduce BLyS-dependent B cell subsets in serologically and clini

185 S receptor, BAFF-R, that resulted in reduced BLyS binding and BLyS-mediated survival.

186 s of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maint

187 Regarding BLyS receptor expression, DCs primarily express cytoplas

188 Regarding BLyS receptor(s) expression, freshly isolated monocytes

189 tudies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting incr

190 -kappaB and NFAT, are involved in regulating BLyS expression through at least one NF-kappaB and 2 NFA

191 therapy targeting the homeostatic regulator, BLyS, may be effective in promoting transplantation tole

192 B cell selection, coupled with the relative BLyS-independence of memory B cells and plasma cells, su

193 The construct rGel/BLyS specifically binds and internalizes through BAFF-R

194 Mechanistically, the rGel/BLyS construct inhibits protein synthesis with an IC(50)

195 n together, these data suggest that the rGel/BLyS fusion toxin may have potential therapeutic efficac

196 This rGel/BLyS-mediated decrease in protein synthesis was associat

197 omain score or 2 new BILAG B domain scores); BLyS levels >/=2 ng/ml (on 2 indices: the SFI and 1 new

198 asma cells are less susceptible to selective BLyS inhibition.

199 Serum BLyS levels were determined by enzyme-linked immunosorbe

200 In every case, serum BLyS levels markedly rose post-BCDT and remained elevate

201 The patterns of B cell depletion, serum BLyS and antibody levels, and clinical relapse for each

202 A decline in serum BLyS levels was associated with the reemergence of B cel

203 ased BCDT leads to marked increases in serum BLyS levels.

204 Our data suggest serum BLyS levels are elevated in patients with familial B-CLL

205 Additionally, we provide evidence that serum BLyS levels are elevated in a subgroup of patients with

206 ysiologically relevant quantities of soluble BLyS, which was dependent on the presence of the pro-pro

207 y analysis of binding of recombinant soluble BLyS to peripheral blood B cells in 36 SLE patients, 29

208 The cytokines B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) enhanc

209 l interactions with B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), the t

210 ssessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reac

211 B lymphocyte stimulator (BLyS) engenders survival and antibody secretion, whereas

212 vival cytokine BAFF/B lymphocyte stimulator (BLyS) has been proposed to participate in the regulation

213 B-lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF) lig

214 B lymphocyte stimulator (BLyS) is a well-known direct costimulator of adaptive im

215 (TNF) family member B lymphocyte stimulator (BLyS) is an important regulator of B cell-dependent auto

216 Serum B lymphocyte stimulator (BLyS) is increased in autoimmune diseases, both in anima

217 protein levels; and B lymphocyte stimulator (BLyS) levels >/=2 ng/ml.

218 Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number

219 with autochthonous B-lymphocyte stimulator (BLyS) ligand in DLBCL cells.

220 The cytokine B lymphocyte stimulator (BLyS) mediates its effect through cell-surface receptors

221 B lymphocyte stimulator (BLyS) protein was found elevated in the serum of endomet

222 teractor (TACI) and B-lymphocyte stimulator (BLyS) provide an early signal critical to generate adequ

223 FcgammaRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling.

224 lar B cells in both B-lymphocyte stimulator (BLyS) receptor expression and BLyS binding capacity, the

225 se in mice, we used B lymphocyte stimulator (BLyS), a cytokine that regulates survival and selection

226 PS and CpG DNA, and B lymphocyte stimulator (BLyS), a key regulator of peripheral B cell survival and

227 B-lymphocyte stimulator (BLyS), a relatively recently recognized member of the tu

228 B lymphocyte stimulator (BLyS), a soluble ligand of the TNF cytokine family, is a

229 nd tolerance is the B-lymphocyte stimulator (BLyS), also referred to as the B-cell activating factor

230 ligand (APRIL) and B-lymphocyte stimulator (BLyS), are important for the survival, proliferation, an

231 rfamily member 13B (B lymphocyte stimulator (BLyS), B cell activating factor (BAFF)) promotes primary

232 TNFSF receptor for B lymphocyte stimulator (BLyS), on CD21(low) B cells was associated with a concom

233 al antibody against B-lymphocyte stimulator (BLyS), showed significant clinical benefit.

234 ll survival factor, B-lymphocyte stimulator (BLyS).

235 mechanism by which B lymphocyte stimulator (BLyS)/BAFF, a tumor necrosis factor superfamily ligand,

236 utralization of the B lymphocyte stimulator (BLyS/BAFF) may enhance the stringency of TR-->FO selecti

237 wth factors such as B lymphocyte stimulator (BLyS; also known as "B-cell factor belonging to the tumo

238 perfamily cytokines B lymphocyte stimulator (BLyS; also known as BAFF) and a proliferation-inducing l

239 s, the GC microenvironment lacks substantial BLyS.

240 ene-encoded, autoreactive BCRs upon systemic BLyS depletion or supplementation, respectively, was obs

241 need for B-cell-DC cooperation through TACI-BLyS during CTL first encounter with antigens in vivo.

242 Several agents that target BLyS are in clinical trials now, and we summarize recent

243 Targeting BLyS as a therapeutic strategy will require overcoming t

244 Additional agents targeting BLyS or other members of this cytokine receptor family a

245 B cell-activating factor (BAFF; also termed BLyS) is essential for B cell generation and maintenance

246 ed in tumors from patients with NHL and that BLyS levels increase as tumors transform to a more aggre

247 We provide evidence that BLyS is expressed in tumors from patients with NHL and t

248 In summary, we found that BLyS and its receptors represent a potentially important

249 Our studies indicate that BLyS is constitutively expressed in aggressive NHL-B cel

250 Our findings indicate that BLyS plays a role in activating innate immune cells.

251 hese results lend support to the notion that BLyS is a candidate for therapeutic targeting in SLE.

252 We propose that BLyS and APRIL regulate B cell as well as T cell functio

253 However, we have reported recently that BLyS is also able to activate monocytes.

254 Here, we show that BLyS alone induces cell-cycle entry and early G(1) cell-

255 We show that BLyS can sustain PC survival in vitro, and this survival

256 In this study, we show that BLyS induces DC activation and maturation.

257 Here, we show that BLyS strongly induces human monocyte survival, and activ

258 Collectively, our data suggest that BLyS may modulate adaptive immune cells indirectly by in

259 mory B cells and plasma cells, suggests that BLyS may be a useful therapeutic target in strategies di

260 The BLyS family of ligands and receptors governs B cell home

261 = 0.0042) and with a greater increase in the BLyS level from the previous visit (P = 0.0007).

262 ssociation between a greater increase in the BLyS level from the previous visit and a greater increas

263 late with the presence of a T at -871 in the BLyS promoter.

264 In both pediatric SLE and JIA, the BLyS expression profiles remained stable at 6 months.

265 absence of correlation between either of the BLyS parameters and disease activity in JIA calls for ci

266 f autoreactive FO B cells independent of the BLyS pathway.

267 g a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -

268 d immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and

269 so termed BAFF), decreased expression of the BLyS receptor 3 (BR3), and altered regulation of PKCdelt

270 flects IL-21-mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium

271 re crucial transcriptional regulators of the BLyS survival pathway in malignant B cells that could be

272 ecause of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls

273 trated that CD40 binds to and stimulates the BLyS/BAFF promoter, another TNF family member (TNFSF-13B

274 iferation-inducing ligand (APRIL), the three BLyS family receptors play central roles in B cell survi

275 Thus, BLyS may be capable of fulfilling APRIL's main functions

276 Thus, BLyS strongly induced up-regulation of surface costimula

277 truct of recombinant gelonin (rGel) fused to BLyS to specifically target quiescent B-CLL lymphocytes.

278 tions of Akt/mTOR and Pim kinase pathways to BLyS-mediated survival.

279 otein levels with disease activity points to BLyS as a candidate therapeutic target in pediatric SLE.

280 the Mcl-1 gene renders B cells refractory to BLyS-mediated protection.

281 protein levels rise and fall in response to BLyS addition and withdrawal, respectively, and conditio

282 e IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not

283 , HIV Nef drives monocyte-derived DCs toward BLyS overexpression through a process involving STAT1.

284 We show that the transient BLyS treatment used in this study substantially affected

285 Whereas in vivo BLyS inhibition profoundly reduced naive B cell numbers

286 Long-term in vivo BLyS neutralization caused an increased TR:FO B cell rat

287 In vivo BLyS neutralization effectively induces humoral toleranc

288 of B lymphocyte-directed therapy via in vivo BLyS neutralization for the prevention of autoimmune dia

289 This study demonstrated that in vivo BLyS neutralization therapy leads to the depletion of fo

290 ll depletion was induced by means of in vivo BLyS neutralization using a murine analog of the monoclo

291 Moreover, in vivo BLyS neutralization: 1) restored negative selection at t

292 When BLyS levels were correlated with response to therapy in

293 del for the pathology of endometriosis where BLyS-responsive plasma cells interact with retrograde me

294 th RA patients and healthy controls, whereas BLyS expression on synovial fluid neutrophils was very l

295 Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lympho

296 nduce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction.

297 In addition, monocytes cultured with BLyS differentiated into macrophage-like cells.

298 ive regulatory functions of FcgammaRIIB with BLyS-mediated B-cell survival.

299 cination only in the subset of patients with BLyS levels in the lowest quartile (P = 0.0003).

300 e entry and G(1) progression in synergy with BLyS, but also DNA replication.