Follicular dendritic cells

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Follicular dendritic cells (FDC) are cells of the

In normal lymphoid tissue, recirculating resting B cells migrate through the FDC networks, whereas antigen-activated B cells are intercepted and undergo clonal expansion within the FDC networks, generating germinal centers (GC). FDCs are among main producers of the chemokine CXCL13 which attracts and organises lymphoid cells.^[11]

Antigen capturing, memory B-cell support

Follicular DCs receptors CR1, CR2 and FcγRIIb trap antigen opsonized by complement or antibodies. These antigens are then taken up in a non-degradative cycling endosomal compartment for later presentation to B cells.^[12] To become selected as a future memory cell, GC B cells must bind the antigen presented on FDCs, otherwise they enter apoptosis.

Debris removal

By secreting the bridging factor MFGE8, which crosslinks apoptotic cells and phagocytes, FDCs promote selective debris removal from the GC.^[13][14]

Preventing autoimmunity

Factor Mfge produced in lymphoid tissues mainly by FDCs is known to enhance engulfment of apoptotic cells. Deficit of this factor in mice leads to a state resembling systemic lupus erythematosus (SLE). Furthermore, mice lacking LT or LT receptors, which are devoid of FDC, develop generalized lymphocytic infiltrates, which are suggestive of autoimmunity. These findings suggest that FDC possibly protect organism against autoimmunity by the removal of potentially self-reactive debris from germinal centres.^[13]

Interaction with B-cells

Noncognate (not antigen specific) B cells play a significant role in the transport of antigens to FDCs. They capture immune complexes in CR1/2-dependent way either directly from the lymph or from macrophages, and move to the lymphoid tissue, where they transfer complement opsonized antigen to the FDCs.^[15][16]

FDCs, in turn, attract B cells with chemoattractant CXCL13. B cells lacking CXCR5, the receptor for CXCL13, still enter the white pulp, but are mislocalized and disorganized. To generate follicular structures, FDCs need to be stimulated by lymphotoxin (LT), a mediator produced by B cells. The stimulation of CXCR5 on B cells upregulates LT production, which leads to FDCs activation and stimulates further CXCL13 secretion, thus generating a positive feed-forward loop. This results in the formation of germinal centers (GCs), where antigen-activated B cells are trapped to undergo somatic mutation, positive and negative selection, isotype switching, and differentiation into high-affinity plasma cells and memory B cells. Adhesion between FDCs and B cells is mediated by ICAM-1 (CD54)–LFA-1 (CD11a) and VCAM–VLA-4 molecules.^[7] Activated B-cells with low affinity to antigen captured on FDCs surface as well as autoreactive B-cells undergo apoptosis,^[17] whereas B cells bound to FDCs through the antigen complex, survive due to apoptosis blockage caused by interaction with FDCs.

Diseases

Rare primary FDC-tumors have been described. These sarcomas often involve lymphoid tissues, but in a number of cases the tumor has been found in the liver, bile duct, pancreas, thyroid, nasopharynx, palatum, submucosa of the stomach or the duodenum. In a number of chronic inflammatory conditions, cells producing CXCL13 chemokine and carrying such FDCs markers as VCAM-1 and CD21, have been observed at quite unexpected sites, including synovial tissue of patients with rheumatoid arthritis (RA), salivary glands of patients with Sjögren’s syndrome, and the skin of patients with pseudo B cells lymphoma.^[7] Follicular dendritic cells participate in HIV-1 infection development both, by providing a haven for HIV-1^[18][19][20] and by stimulating HIV-1 replication in adjacent infected monocytic cells via a juxtacrine signaling mechanism.^[21] There is also some evidence, that FDCs may promote prion replication and neuroinvasion in neuroinvasive scrapie.^[22]

See also

• Follicular+Dendritic+Cells at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

References

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