Lymph node stromal cell

Source: Wikipedia, the free encyclopedia.

Lymph node stromal cells are essential to the structure and function of the

hematopoietic cells; the release of small molecule chemical messengers that facilitate interactions between hematopoietic cells; the facilitation of the migration of hematopoietic cells; the presentation of antigens to immune cells at the initiation of the adaptive immune system; and the homeostasis of lymphocyte numbers.[1] Stromal cells originate from multipotent mesenchymal stem cells.[2]

Structure

Main article: Lymph node § Structure
Diagram of a lymph node.

Lymph nodes are enclosed in an external

macrophages (specialised cells which help to keep the extracellular matrix
in order).

The interior of the lymph node has two regions: the

stromal
cells.

Near the medulla is the

Lymph vessels entering the node do so along the perimeter (outer surface).[3]

Function

Histological section of a normal lymph node
Lymphocyte surrounded by red blood cells.

The lymph nodes, the

hematopoietic cells are important for the development of lymph nodes. Crosstalk LEC, lymphoid tissue inducer cells and mesenchymal stromal organizer cells initiate the formation of lymph nodes.[1]

Naive lymphocytes (those with no history of contact with

lymphoblasts, to lymph nodes, where they mature.[5]

The primary role of lymph node stromal cells is structural. They form a scaffold for hematopoietic cells and assist their movement along it. The molecular signaling systems (

chemokines) that distribute lymphocytes to appropriate localities within the lymph node (T and B cell segregation) are also created by lymph node stromal cells. Lymphocytes have receptors for such chemokines. For example, Naive T cells express the CCR7 receptor for the chemokine CCL21.[1] and B cells exhibit CXCR5 receptors for chemokine CXCL13
.

The lymph from the peripheral tissues contains soluble

dendritic cells
.

In an inflammatory state, lymphatic endothelial cells increase their surface adhesion molecules, and dendritic cells express a surface

CLEC-2
), which bind to gp38 on the surface of lymphatic endothelial cells.

Lymphocytes leave the lymph node, as effector immune cells, via the

efferent lymph vessels. Their numbers compensate for the removal of dead peripheral lymphocytes.[4] B and T lymphocytes leave the lymph node based on changes in concentration of sphingosine-1-phosphate (S1P). The concentration of S1P in the lymph node is maintained at a level lower than that of the blood or the lymph under the influence of S1P lyase. This means immune cells may leave the lymph node along a chemokine gradient.[6]

Most T cells are, in time, eliminated in the thymus by a process of clonal deletion. However, some of them escape this process and are then "mopped up" in the lymph nodes. Lymph node stromal cells express peripheral tissue-restricted antigens (PTAs) on their surface. The Transcription factor Aire (autoimmune regulator) that controls the expression of PTAs on mTEC cells in the thymus is only expressed at low levels by uncharacterized double negative stromal cells. Most lymph node stromal cells preferentially express DF1, an Aire-like transcription modulator.[1]

Types of lymph node stromal cells

Lymph node stromal cells can be grouped into six sub-populations, known by their expression of

MAdCAM-1).[1]

Surface markers
CD 31 + CD 31 - GP 38 + GP 38 - ITGA7 +
FRC[6] No Yes Yes No -
FDC No Yes Yes Yes -
LEC Yes No Yes No -
BEC Low - No Yes -
AIP No Yes No Yes Yes
DNC - - - - -

Fibroblastic reticular cells

Fibroblastic reticular cells (FRCs) are located in the T cell zone of the cortex. FRCs produce collagen alpha-1(III) rich reticular fibers that form a dense network within the lymphoid tissue. These are connected by collagen XIV, small leucine-rich proteoglycans and lysyl oxidase. The network of fibers supports and guides the movement of dendritic cells (DCs), T lymphocytes and B lymphocytes.[1] It also creates a porous molecular sieve in the lymph node.

The lymph carries

CCR7
receptors.

FRCs also produce components of extracellular matrix, such as

α-actin smooth muscle that may influence the formation of the reticular fiber network.[6] For example, the chemokine CCL21 attaches to the surface of the FRCs through collagen and glycosaminoglycan molecules.[4]

FRCs express cytokine IL-7, a regulator of the survival of resting T lymphocytes.

Follicular dendritic cells

CD35
and complement components. The network of cellular filaments and receptors help the FDCs capture antigens as immune complexes and present them to other immune cells.

FDCs assist the development of the

B lymphocytes to the primary B cell follicle.[4] B lymphocytes need a factor B cell activating factor (BAFF) for their survival, also produced by FDCs.[6]

Marginal reticular cells

Marginal reticular cells (MRCs) form a layer of cells beneath the

tumor necrosis factor. They are one of organizer cells involved in the formation of the structure of lymph node during organogenesis. They express CXCL13 at the edges of B cell follicles.[6]

Lymphatic endothelial cells

adhesion molecules on the surfaces of LECs increase.[4]

High endothelial cells

High endothelial cells (HECs) are specialized vascular

endothelial cells. In the thymus, they line the high endothelial venules (HEVs) where lymphocytes originate. The HEVs of the lymph node express adhesion molecules like peripheral node addressin (PNAd) that are essential for the migration of naive T cells from the peripheral blood to the lymph node.[7] In mouse lymph nodes the HECs also express the chemokine CCL21 which will bind its receptor CCR7 on the naive T-cell and enhance the migration.[7][8]

Alpha-7 integrin pericytes

heterodimers. Integrin chains allow integrin pericytes to interact with hematopoietic cells and promote their migration.[1]

Malignancy

Lymph node stromal cells can give rise to a number of malignancies including: follicular dendritic cell sarcoma; fibroblastic reticular cell sarcoma; inflammatory myofibroblastic tumours and others.[9]

In addition, lymph node stromal cells may produce growth factors which actively contribute to tumour cell metastasis.[10]

References

  1. ^
    PMID 23278748
    .
  2. ^ Mebius R. "Stromal immunology group inaugural meeting." Archived 2014-04-13 at the Wayback Machine British Society for Immunology website 15 March 2012. Accessed 20 March 2014.
  3. ^ Cihak R. "Anatomie." Grada publishing 1997, first edition.
  4. ^
    PMID 23060882
    .
  5. ^
    PMID 22466668
    .
  6. ^
    PMID 19644499
    .
  7. ^
    PMID 19644499
    .
  8. PMID 9585422
    .
  9. ISBN 1607613840
    , 9781607613848. Accessed 20 March 2014.
  10. ^ Lebedis c. et al "Peripheral lymph node stromal cells can promote growth and tumorigenicity of breast carcinoma cells through the release of IGF-1 and EGF." Int. J. Cancer 2002 100 p2 - 8 Accessed 20 March 2014.
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