Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells.

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Research Abstract Details 

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Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Abstract Text:

Crosslinking the CD27 antigen on T cells provides a costimulatory signal that, in concert with T-cell receptor crosslinking, can induce T-cell proliferation and cellular immune activation. We find that chronic lymphocytic leukemia (CLL) B cells from most patients coexpress both membrane-bound and soluble CD27, along with its newly identified ligand, CD70. The expression of soluble CD27 may preclude leukemic B cells from stimulating T cells via CD70, thereby potentially impairing their ability to function as effective antigen-presenting cells. We find that leukemic B-cell expression of soluble and membrane-bound CD27 can be downmodulated through a CD40-dependent signal. This signal also induces enhanced expression of CD70 on both normal and leukemic B cells. We find that tumor necrosis factor (TNF)-alpha, or the Th1 cytokine interferon (IFN)-gamma, also can induce downmodulation of CD27, whereas Th2-associated cytokines interleukin-4 (IL-4) or IL-10 can enhance leukemic B-cell expression of this accessory molecule. The modulation of CD27 induced by these conditions is accompanied by reciprocal changes in the expression levels of CD70, suggesting that these accessory molecules may be engaged in reciprocal receptor-ligand downmodulation. Consistent with this, we observe that co-culture of CLL B cells with transfected murine plasmacytoma cells that express human CD70 affects downmodulation of CD27 and enhanced expression of CD70 on leukemic B cells, but does not affect expression of CD27 mRNA. However, we find that CD40-crosslinking, in addition to reducing the level of CD27 protein, also reduces leukemic B-cell expression of CD27 mRNA. This argues that the changes in the expression levels of CD27 following CD40-signaling are not simply due to induced increases in the expression levels of CD70. Finally, we demonstrate that reciprocal changes in expression of CD27 and CD70 may contribute to the enhanced antigen-presenting capacity of CLL B cells after CD40-dependent leukemic B-cell activation. These findings expand the understanding of the regulation of costimulatory molecules important in antigen presentation and also have implications for the immunobiology of and therapy for CLL.

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Publishing Authors By Initials

For similar cells: cells, cultured: tumor cells, cultured research abstracts see: cells: cells, cultured: tumor cells, cultured research

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MEDLINE DATE:

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Blood

VOLUME: 85

Page Numbers: 3556-65

Journal Abbreviation: Blood

ISSN: 0006-4971

DAY: 15

MONTH: Jun

YEAR: 1995

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7603509

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Keywords Mesh Terms:

KEYWORDS: Tumor Cells, Cultured

MESH TERMS: biosynthesis

Chemical & Substance for Abstract: Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells. Information

Substance Name: Membrane Proteins

Registry Number: 0

Grant and Affiliation Information for Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells.

AFFILIATION: Department of Medicine, University of California San Diego, La Jolla 92093-0663, USA.

Country: UNITED STATES

AGENCY: United States NCI

GRANT: CA49870

ACRONYM: CA

MEDLINETA: Blood

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