Role of Zinc Signaling in Mast Cell, Basophil, T Cell, and B Cell

Zinc is essential for maintaining normal structure and physiological function of cells. Its deficiency causes growth retardation, immunodeficiency, and neuronal degeneration. Zinc homeostasis is tightly regulated by zinc transporters and metallothioneins that control zinc concentration and its distribution in individual cells and contributes to zinc signaling. The intracellular zinc signaling regulates immune reactions. Although many molecules involved in these processes have zinc-binding motifs, the molecular mechanisms and the role of zinc in immune responses have not been elucidated. We and others have demonstrated that zinc signaling plays diverse and specific rolesin vivoandin vitroin studies using knockout mice lacking zinc transporter function and metallothionein function. In this review, we discuss the impact of zinc signaling focusing particularly on mast cell-, basophil-, and T cell-mediated inflammatory and allergic responses. We also describe zinc signaling dysregulation as a leading health problem in inflammatory disease and allergy.

Download Full-text

Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

eLife ◽

10.7554/elife.19552 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 20

Author(s):

Ting-ting Zhang ◽

David G Gonzalez ◽

Christine M Cote ◽

Steven M Kerfoot ◽

Shaoli Deng ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Germinal Center ◽

B Cell Differentiation ◽

B Cell Maturation ◽

Germinal Center B Cell ◽

T Cell Help ◽

Dose Dependent

To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.

Download Full-text

T-cell and mast cell lines respond to B-cell stimulatory factor 1.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.83.15.5654 ◽

1986 ◽

Vol 83 (15) ◽

pp. 5654-5658 ◽

Cited By ~ 212

Author(s):

T. R. Mosmann ◽

M. W. Bond ◽

R. L. Coffman ◽

J. Ohara ◽

W. E. Paul

Keyword(s):

Mast Cell ◽

T Cell ◽

B Cell ◽

Cell Lines ◽

Stimulatory Factor

Download Full-text

Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19

Journal of Experimental Medicine ◽

10.1084/jem.188.1.145 ◽

1998 ◽

Vol 188 (1) ◽

pp. 145-155 ◽

Cited By ~ 49

Author(s):

Thomas Fehr ◽

Robert C. Rickert ◽

Bernhard Odermatt ◽

Jürgen Roes ◽

Klaus Rajewsky ◽

...

Keyword(s):

T Cell ◽

B Cells ◽

B Cell ◽

Cell Activation ◽

Antibody Responses ◽

B Cell Activation ◽

Protein Antigens ◽

Cell Memory ◽

B Cell Memory

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene–targeted mice revealed that T cell–dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell–independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19−/− mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19−/− mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.

Download Full-text

THE ROLE OF THE I-REGION IN THE CONTROL OF MACROPHAGE-T CELL AND T CELL-B CELL INTERACTIONS

Cell Biology and Immunology of Leukocyte Function ◽

10.1016/b978-0-12-569650-0.50054-1 ◽

1979 ◽

pp. 397-402

Author(s):

Uki Yamashita ◽

Ethan M. Shevach

Keyword(s):

T Cell ◽

B Cell ◽

Cell Interactions

Download Full-text

T-cell regulation of human B-cell activation. A reappraisal of the role of interleukin 2

Immunology Today ◽

10.1016/0167-5699(85)90061-1 ◽

1985 ◽

Vol 6 (9) ◽

pp. 258-259 ◽

Cited By ~ 20

Author(s):

Frank Miedema ◽

Cornelis J.M. Melief

Keyword(s):

T Cell ◽

B Cell ◽

Cell Activation ◽

Interleukin 2 ◽

B Cell Activation ◽

Cell Regulation ◽

T Cell Regulation ◽

Human B Cell

Download Full-text

Delta-Like-1 Changes the Immunomodulatory Property of OP9 Cells

Stem Cells International ◽

10.1155/2016/1628352 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11

Author(s):

Lei Zhang ◽

Rui-Jie Dang ◽

Yan-Mei Yang ◽

Dian-Chao Cui ◽

Ping Li ◽

...

Keyword(s):

Cell Proliferation ◽

T Cell ◽

B Cell ◽

Stromal Cells ◽

B Lymphocyte ◽

B Cell Development ◽

T Cell Proliferation ◽

No Production ◽

Immunomodulatory Property

As stromal cells and recently confirmed mesenchymal stem cells, OP9 cells support hematopoiesis stem cell (HSC) differentiation into the B lymphocyte lineage, yet Delta-like-1 (DL1) overexpressing OP9 (OP9DL1) cells promote the development of early T lymphocytes from HSC. However, the immunomodulatory capacity of OP9 or OP9DL1 on mature B and T cell proliferation has not been elucidated. Here, we show that OP9 and OP9DL1 have similar proliferation capacities and immunophenotypes except DL1 expression. Compared with OP9, OP9DL1 displayed more osteogenesis and less adipogenesis when cultured in the respective induction media. Both OP9 and OP9DL1 inhibited mature B and T cell proliferation. Furthermore, OP9 showed stronger inhibition on B cell proliferation and OP9DL1 exhibited stronger inhibition on T cell proliferation. With stimulation, both OP9 and OP9DL1 showed increased nitrate oxide (NO) production. The NO levels of OP9 were higher than that of OP9DL1 when stimulated with TNFα/IFNγor LPS/IL4. Taken together, our study reveals a previously unrecognized role of OP9 and OP9DL1 in mature B and T cell proliferation. DL1 overexpression alone changed the properties of OP9 cells in addition to their role in early B cell development.

Download Full-text