page_title: Lupus
section_title: Germinal centers
hierarchical_section_title: Lupus / Pathophysiology / Germinal centers
caption_attribution_description: Germinal centres of SLE patients and controls (schematic). Red: CD68 in tingible body macrophages; black: TUNEL positive apoptotic cells. Healthy donors with florid germinal centres show giant tingible body macrophages (TBM) containing ingested apoptotic cells and no uningested apoptotic cells outside the TBM. Patients with follicular lymphoma show small tingible body macrophages (TBM) containing few ingested apoptotic cells however, there are no uningested apoptotic cells outside the TBM. Some patients with SLE (1) show lack of TBM and many uningested apoptotic cells decorating the surfaces of spindle-shaped cell, presumably follicular dendritic cells (SLE 1). Some few patients with SLE show TBM containing few ingested apoptotic cells and many uningested apoptotic cells outside the TBM (SLE 2). However, about 50&#160;% of the SLE patients show are rather normal germinal centre.
context_page_description: Lupus, technically known as systemic lupus erythematosus, is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary between people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission during which there are few symptoms.
  The cause of SLE is not clear. It is thought to involve genetics together with environmental factors. Among identical twins, if one is affected there is a 24% chance the other one will be as well. Female sex hormones, sunlight, smoking, vitamin D deficiency, and certain infections are also believed to increase the risk. The mechanism involves an immune response by autoantibodies against a person's own tissues. These are most commonly anti-nuclear antibodies and they result in inflammation. Diagnosis can be difficult and is based on a combination of symptoms and laboratory tests.
context_section_description: In healthy conditions, apoptotic lymphocytes are removed in germinal centers (GC) by specialized phagocytes, the tingible body macrophages (TBM), which is why no free apoptotic and potential autoantigenic material can be seen. In some people with SLE, buildup of apoptotic debris can be observed in GC because of an ineffective clearance of apoptotic cells. In close proximity to TBM, follicular dendritic cells (FDC) are localised in GC, which attach antigen material to their surface and, in contrast to bone marrow-derived DC, neither take it up nor present it via MHC molecules.
  Autoreactive B cells can accidentally emerge during somatic hypermutation and migrate into the germinal center light zone. Autoreactive B cells, maturated coincidentally, normally do not receive survival signals by antigen planted on follicular dendritic cells and perish by apoptosis. In the case of clearance deficiency, apoptotic nuclear debris accumulates in the light zone of GC and gets attached to FDC. This serves as a germinal centre survival signal for autoreactive B-cells. After migration into the mantle zone, autoreactive B cells require further survival signals from autoreactive helper T cells, which promote the maturation of autoantibody-producing plasma cells and B memory cells. In the presence of autoreactive T cells, a chronic autoimmune disease may be the consequence.
caption: Germinal centres in a person with SLE and controls (schematic). Red: CD68 in tingible body macrophages; black: TUNEL positive apoptotic cells. 1) Healthy donors with florid germinal centres show giant tingible body macrophages (TBM) containing ingested apoptotic cells and no uningested apoptotic cells outside the TBM. 2) People with follicular lymphoma show small tingible body macrophages (TBM) containing few ingested apoptotic cells however, there are no uningested apoptotic cells outside the TBM. 3) Some with SLE (1) show lack of TBM and many uningested apoptotic cells decorating the surfaces of spindle-shaped cell, presumably follicular dendritic cells (SLE 1). 4) Some people with SLE show TBM containing few ingested apoptotic cells and many uningested apoptotic cells outside the TBM (SLE 2). However, about 50 % of people with SLE show rather normal germinal centre.
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