scholarly journals FcγRIIB signals inhibit BLyS signaling and BCR-mediated BLyS receptor up-regulation

Blood ◽  
2009 ◽  
Vol 113 (7) ◽  
pp. 1464-1473 ◽  
Author(s):  
Jenni E. Crowley ◽  
Jason E. Stadanlick ◽  
John C. Cambier ◽  
Michael P. Cancro
Keyword(s):  
B Cell ◽  
Cell Survival ◽  
B Lymphocyte ◽  
Binding Capacity ◽  
Src Homology 2 ◽  
B Cell Survival ◽  
B Lymphocyte Stimulator ◽  
Src Homology ◽  
Optimal Action ◽  
Regulatory Functions

Abstract These studies investigate how interactions between the BCR and FcγRIIB affect B lymphocyte stimulator (BLyS) recep-tor expression and signaling. Previous studies showed that BCR ligation up-regulates BLyS binding capacity in mature B cells, reflecting increased BLyS receptor levels. Here we show that FcγRIIB coaggregation dampens BCR-induced BLyS receptor up-regulation. This cross-regulation requires BCR and FcγRIIB coligation, and optimal action relies on the Src-homology-2 (SH2)–containing inositol 5 phosphase-1 (SHIP1). Subsequent to FcγRIIB/BCR coaggregation, the survival promoting actions of BLyS are attenuated, reflecting reduced BLyS receptor signaling capacity in terms of Pim 2 maintenance, noncanonical NF-κB activation, and Bcl-xL levels. These findings link the negative regulatory functions of FcγRIIB with BLyS-mediated B-cell survival.

scholarly journals Attenuation of Apoptosis Underlies B Lymphocyte Stimulator Enhancement of Humoral Immune Response

2000 ◽  
Vol 192 (7) ◽  
pp. 953-964 ◽  
Author(s):  
Richard K.G. Do ◽  
Eunice Hatada ◽  
Hayyoung Lee ◽  
Michelle R. Tourigny ◽  
David Hilbert ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
B Lymphocyte ◽  
Humoral Immune ◽  
B Cell Survival ◽  
B Lymphocyte Stimulator

B lymphocyte stimulator (BLyS) is a newly identified monocyte-specific TNF family cytokine. It has been implicated in the development of autoimmunity, and functions as a potent costimulator with antiimmunoglobulin M in B cell proliferation in vitro. Here we demonstrate that BLyS prominently enhances the humoral responses to both T cell–independent and T cell–dependent antigens, primarily by attenuation of apoptosis as evidenced by the prolonged survival of antigen-activated B cells in vivo and in vitro. BLyS acts on primary splenic B cells autonomously, and directly cooperates with CD40 ligand (CD40L) in B cell activation in vitro by protecting replicating B cells from apoptosis. Moreover, although BLyS alone cannot activate the cell cycle, it is sufficient to prolong the survival of naive resting B cells in vitro. Attenuation of apoptosis by BLyS correlates with changes in the ratios between Bcl-2 family proteins in favor of cell survival, predominantly by reducing the proapoptotic Bak and increasing its prosurvival partners, Bcl-2 and Bcl-xL. In either resting or CD40L-activated B cells, the NF-κB transcription factors RelB and p50 are specifically activated, suggesting that they may mediate BLyS signals for B cell survival. Together, these results provide direct evidence for BLyS enhancement of both T cell–independent and T cell–dependent humoral immune responses, and imply a role for BLyS in the conservation of the B cell repertoire. The ability of BLyS to increase B cell survival indiscriminately, at either a resting or activated state, and to cooperate with CD40L, further suggests that attenuation of apoptosis underlies BLyS enhancement of polyclonal autoimmunity as well as the physiologic humoral immune response.

scholarly journals A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice

Blood ◽  
2011 ◽  
Vol 118 (5) ◽  
pp. 1294-1304 ◽  
Author(s):  
Yi Hao ◽  
Patrick O'Neill ◽  
Martin S. Naradikian ◽  
Jean L. Scholz ◽  
Michael P. Cancro
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocyte ◽  
Binding Capacity ◽  
Cell Subset ◽  
Receptor Expression ◽  
Cd40 Stimulation ◽  
B Lymphocyte Stimulator ◽  
Cell Niche ◽  
B Cell Subsets

Abstract We have discovered a distinct mature B-cell subset that accumulates with age, which we have termed age-associated B cells. These cells comprise up to 30% of mature B cells by 22 months. Despite sharing some features with other mature B-cell subsets, they are refractory to BCR and CD40 stimulation. Instead, they respond to TLR9 or TLR7 stimulation and divide maximally on combined BCR and TLR ligation, leading to Ig production and preferential secretion of IL-10 and IL-4. Although similar to follicular B cells in both B-lymphocyte stimulator (BLyS) receptor expression and BLyS binding capacity, these cells do not rely on BLyS for survival. They are neither cycling nor the result of intrinsically altered B lymphopoiesis in aged BM, but instead appear to be generated from mature B cells that exhaustively expand during the individual's lifetime. Finally, they present Ag effectively and favor polarization to a TH17 profile. Together, these findings reveal that while the magnitude of the mature primary B-cell niche is maintained with age, it is increasingly occupied by cells refractory to BCR-driven activation yet responsive to innate receptor stimulation.

BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complex

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2257-2265 ◽  
Author(s):  
Hidenori Hase ◽  
Yumiko Kanno ◽  
Masaru Kojima ◽  
Kaoru Hasegawa ◽  
Daisuke Sakurai ◽  
...  
Keyword(s):  
B Cell ◽  
B Lymphocyte ◽  
Protein Activity ◽  
Cell Responses ◽  
Surface Molecules ◽  
B Cell Survival ◽  
B Lymphocyte Stimulator ◽  
Interleukin 15 ◽  
Necrosis Factor ◽  
Cell Survival Factor

Abstract The tumor necrosis factor (TNF)–like ligand BAFF/BLyS (B-cell activating factor of the TNF family/B-lymphocyte stimulator) is a potent B-cell survival factor, yet its functional relationship with other B-cell surface molecules such as CD19 and CD40 is poorly understood. We found that follicular dendritic cells (FDCs) in human lymph nodes expressed BAFF abundantly. BAFF up-regulated a B cell–specific transcription factor Pax5/BSAP (Pax5/B cell–specific activator protein) activity and its target CD19, a major component of the B-cell coreceptor complex, and synergistically enhanced CD19 phosphorylation by B-cell antigen receptor (BCR). BAFF further enhanced B-cell proliferation, immunoglobulin G (IgG) production, and reactivity to CD154 by BCR/CD19 coligation and interleukin-15 (IL-15). Our results suggest that BAFF may play an important role in FDC–B-cell interactions through the B-cell coreceptor complex and a possibly sequential link between the T cell–independent and –dependent B-cell responses in the germinal centers.

Factors from fibroblasts promote pancreatic islet B cell survival in tissue culture

Diabetes ◽  
1979 ◽  
Vol 28 (12) ◽  
pp. 1108-1113 ◽  
Author(s):  
A. Rabinovitch ◽  
T. Russell ◽  
D. H. Mintz
Keyword(s):  
Tissue Culture ◽  
B Cell ◽  
Cell Survival ◽  
Pancreatic Islet ◽  
B Cell Survival

scholarly journals Ras Mediates Effector Pathways Responsible for Pre-B Cell Survival, Which Is Essential for the Developmental Progression to the Late Pre-B Cell Stage

2000 ◽  
Vol 192 (2) ◽  
pp. 171-182 ◽  
Author(s):  
Hitoshi Nagaoka ◽  
Yoshimasa Takahashi ◽  
Reiko Hayashi ◽  
Tohru Nakamura ◽  
Kumiko Ishii ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Survival ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Antigen Receptors ◽  
Cell Stage ◽  
Light Chain Gene ◽  
B Cell Survival ◽  
Effector Pathways

Ras is essential for the transition from early B cell precursors to the pro-B stage, and is considered to be involved in the signal cascade mediated by pre-B cell antigen receptors. To examine the role of p21ras in the late stage of B cell differentiation, we established transgenic mice (TG) expressing a dominant-inhibitory mutant of Ha-ras (Asn-17 Ha-ras) in B lineage cells at high levels after the early B cell precursor stage. Expression of p21Asn-17 Ha-ras was associated with a prominent reduction in the number of late pre-B cells, but had little effect on proliferation of early pre-B cells. Inhibition of p21ras activity markedly reduced the life span of pre-B cells, due, at least in part, to downregulation of the expression of an antiapoptotic protein, Bcl-xL. Thus, the apparent role for p21ras activity in pre-B cell survival may explain the decreased numbers of late pre-B cells in Asn-17 Ha-ras TG. Consistent with this possibility, overexpression of Bcl-2 in Asn-17 Ha-ras TG reversed the reduction in the number of late pre-B cells undergoing immunoglobulin light chain gene (IgL) rearrangement and progressing to immature B cells. These results suggest that p21ras mediates effector pathways responsible for pre-B cell survival, which is essential for progression to the late pre-B and immature B stages.

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