scholarly journals TGFβ Superfamily Members as Regulators of B Cell Development and Function—Implications for Autoimmunity

2018 ◽  
Vol 19 (12) ◽  
pp. 3928 ◽  
Author(s):  
Esther Tamayo ◽  
Pilar Alvarez ◽  
Ramón Merino
Keyword(s):  
B Cell ◽  
Cell Fate ◽  
Cell Development ◽  
B Cell Development ◽  
Postnatal Life ◽  
Potential Contribution ◽  
Cellular Processes ◽  
New Findings ◽  
And Function ◽  
Tgfβ Superfamily

The TGFβ superfamily is composed of more than 33 growth and differentiation factors, including TGFβ1, β2, β3, BMPs, GDFs, nodal-related proteins, and activins. These members usually exert pleiotropic actions on several tissues and control multiple cellular processes, such as cell growth, cell survival, cell migration, cell fate specification, and differentiation, both during embryonic development and postnatal life. Although the effects of these factors on immune responses were elucidated long ago, most studies have been focused on the actions of TGFβs on T cells, as major regulators of adaptive immunity. In this review, we discuss new findings about the involvement of TGFβ superfamily members in the control of B cell development and function. Moreover, the potential contribution of TGFβ signaling to control B cell-mediated autoimmune diseases and its utility in the design of new therapies are also discussed.

Loss of IP3 Receptor–Mediated Ca2+ Release in Mouse B Cells Results in Abnormal B Cell Development and Function

2017 ◽  
Vol 199 (2) ◽  
pp. 570-580 ◽  
Author(s):  
Huayuan Tang ◽  
Hong Wang ◽  
Qingsong Lin ◽  
Feifei Fan ◽  
Fei Zhang ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
Ip3 Receptor ◽  
And Function

scholarly journals Regulation of B-cell development and function by microRNAs

2013 ◽  
Vol 253 (1) ◽  
pp. 25-39 ◽  
Author(s):  
Virginia G de Yébenes ◽  
Nahikari Bartolomé-Izquierdo ◽  
Almudena R. Ramiro
Keyword(s):  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
And Function

scholarly journals Essential Immunoregulatory Role for BCAP in B Cell Development and Function

2002 ◽  
Vol 195 (5) ◽  
pp. 535-545 ◽  
Author(s):  
Tetsuo Yamazaki ◽  
Kiyoshi Takeda ◽  
Kumiko Gotoh ◽  
Hiroshi Takeshima ◽  
Shizuo Akira ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Cell Development ◽  
B Cell Development ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Phosphoinositide 3 Kinase ◽  
And Function ◽  
B Cell Deficiency

BCAP was recently cloned as a binding molecule to phosphoinositide 3-kinase (PI3K). To investigate the role of BCAP, mutant mice deficient in BCAP were generated. While BCAP-deficient mice are viable, they have decreased numbers of mature B cells and B1 B cell deficiency. The mice produce lower titers of serum immunoglobulin (Ig)M and IgG3, and mount attenuated responses to T cell–independent type II antigen. Upon B cell receptor cross-linking, BCAP-deficient B cells exhibit reduced Ca2+ mobilization and poor proliferative responses. These findings demonstrate that BCAP plays a pivotal immunoregulatory role in B cell development and humoral immune responses.

scholarly journals Germline-activating mutations in PIK3CD compromise B cell development and function

2018 ◽  
Vol 215 (8) ◽  
pp. 2073-2095 ◽  
Author(s):  
Danielle T. Avery ◽  
Alisa Kane ◽  
Tina Nguyen ◽  
Anthony Lau ◽  
Akira Nguyen ◽  
...  
Keyword(s):  
B Cell ◽  
Cytidine Deaminase ◽  
Pathogenic Mutation ◽  
Gene Signature ◽  
Cell Development ◽  
B Cell Development ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Class Switch ◽  
And Function

Gain-of-function (GOF) mutations in PIK3CD, encoding the p110δ subunit of phosphatidylinositide 3-kinase (PI3K), cause a primary immunodeficiency. Affected individuals display impaired humoral immune responses following infection or immunization. To establish mechanisms underlying these immune defects, we studied a large cohort of patients with PIK3CD GOF mutations and established a novel mouse model using CRISPR/Cas9-mediated gene editing to introduce a common pathogenic mutation in Pik3cd. In both species, hyperactive PI3K severely affected B cell development and differentiation in the bone marrow and the periphery. Furthermore, PI3K GOF B cells exhibited intrinsic defects in class-switch recombination (CSR) due to impaired induction of activation-induced cytidine deaminase (AID) and failure to acquire a plasmablast gene signature and phenotype. Importantly, defects in CSR, AID expression, and Ig secretion were restored by leniolisib, a specific p110δ inhibitor. Our findings reveal key roles for balanced PI3K signaling in B cell development and long-lived humoral immunity and memory and establish the validity of treating affected individuals with p110δ inhibitors.

Transcriptional control of B cell development and function

Gene ◽  
2004 ◽  
Vol 327 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Boris Bartholdy ◽  
Patrick Matthias
Keyword(s):  
B Cell ◽  
Transcriptional Control ◽  
Cell Development ◽  
B Cell Development ◽  
And Function

scholarly journals bcl-x exhibits regulated expression during B cell development and activation and modulates lymphocyte survival in transgenic mice.

1996 ◽  
Vol 183 (2) ◽  
pp. 381-391 ◽  
Author(s):  
D A Grillot ◽  
R Merino ◽  
J C Pena ◽  
W C Fanslow ◽  
F D Finkelman ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Cell Lineage ◽  
Cell Development ◽  
B Cell Development ◽  
Immunoglobulin M ◽  
Protective Mechanism ◽  
And Function ◽  
Peripheral B Cells

We have assessed during B cell development, the regulation and function of bcl-x, a member of the bcl-2 family of apoptosis regulatory genes. Here we show that Bcl-xL, a product of bcl-x, is expressed in pre-B cells but downregulated at the immature and mature stages of B cell development. Bcl-xL but not Bcl-2 is rapidly induced in peripheral B cells upon surface immunoglobulin M (IgM) cross-linking, CD40 signaling, or LPS stimulation. Transgenic mice that overexpressed Bcl-xL within the B cell lineage exhibited marked accumulation of peripheral B cells in lymphoid organs and enhanced survival of developing and mature B cells. B cell survival was further increased by simultaneous expression of bcl-xL and bcl-2 transgenes. These studies demonstrate that Bcl-2 and Bcl-xL are regulated differentially during B cell development and activation of mature B cells. Induction of Bcl-xL after signaling through surface IgM and CD40 appears to provide mature B cells with an additional protective mechanism against apoptotic signals associated with antigen-induced activation and proliferation.

scholarly journals Cutting Edge: Essential Role of Phospholipase C-γ2 in B Cell Development and Function

2000 ◽  
Vol 165 (4) ◽  
pp. 1738-1742 ◽  
Author(s):  
Ari Hashimoto ◽  
Kiyoshi Takeda ◽  
Muneo Inaba ◽  
Masayuki Sekimata ◽  
Tsuneyasu Kaisho ◽  
...  
Keyword(s):  
B Cell ◽  
Phospholipase C ◽  
Essential Role ◽  
Cell Development ◽  
B Cell Development ◽  
Cutting Edge ◽  
And Function

scholarly journals Iκb Kinase α Is Essential for Mature B Cell Development and Function

2001 ◽  
Vol 193 (4) ◽  
pp. 417-426 ◽  
Author(s):  
Tsuneyasu Kaisho ◽  
Kiyoshi Takeda ◽  
Tohru Tsujimura ◽  
Taro Kawai ◽  
Fumiko Nomura ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Fetal Liver ◽  
Cell Development ◽  
B Cell Development ◽  
Cytokine Signaling ◽  
Iκb Kinase ◽  
And Function

IκB kinase (IKK) α and β phosphorylate IκB proteins and activate the transcription factor, nuclear factor (NF)-κB. Although both are highly homologous kinases, gene targeting experiments revealed their differential roles in vivo. IKKα is involved in skin and limb morphogenesis, whereas IKKβ is essential for cytokine signaling. To elucidate in vivo roles of IKKα in hematopoietic cells, we have generated bone marrow chimeras by transferring control and IKKα-deficient fetal liver cells. The mature B cell population was decreased in IKKα−/− chimeras. IKKα−/− chimeras also exhibited a decrease of serum immunoglobulin basal level and impaired antigen-specific immune responses. Histologically, they also manifested marked disruption of germinal center formation and splenic microarchitectures that depend on mature B cells. IKKα−/− B cells not only showed impairment of survival and mitogenic responses in vitro, accompanied by decreased, although inducible, NF-κB activity, but also increased turnover rate in vivo. In addition, transgene expression of bcl-2 could only partially rescue impaired B cell development in IKKα−/− chimeras. Taken together, these results demonstrate that IKKα is critically involved in the prevention of cell death and functional development of mature B cells.

OCA-B regulation of B-cell development and function

2003 ◽  
Vol 24 (10) ◽  
pp. 546-553 ◽  
Author(s):  
Michael A. Teitell
Keyword(s):  
B Cell ◽  
Cell Development ◽  
B Cell Development ◽  
And Function
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