Plasma cells, also called plasma B cells, plasmocytes, plasmacytes, or effector B cells, are white blood cells that secrete large volumes of antibodies. They are transported by the blood plasma and the lymphatic system. Plasma cells originate in the bone marrow; B cells differentiate into plasma cells that produce antibody molecules closely modelled after the receptors of the precursor B cell. Once released into the blood and lymph, these antibody molecules bind to the target antigen (foreign substance) and initiate its neutralization or destruction.

The clinical presentation of primary PCL (pPCL) indicates a far more aggressive disease than that of a typical multiple myeloma case with its clinical features being a combination of those found in multiple myeloma and acute leukemia. Like multiple myeloma patients, pPCL patients exhibit pathologically high levels of monoclonal plasma cells in their bone marrow plus a malignant plasma cell-secreted circulating monoclonal myeloma protein, either IgG, IgA, a light chain, or none in 28-56%, 4-7%, 23-44%, or 0-12% of cases, respectively. Similar to B cell leukemias, but unlike multiple myeloma, pPCL patients exhibit relative high frequencies of splenomegaly, lymphadenopathy, hepatomegaly, kidney failure, bone marrow failure (i.e. thrombocytopenia, anemia, and/or, rarely, leukopenia), central nervous system defects, and peripheral neuropathies due to the invasion of these tissues by plasma cells and/or the deposition of their circulating monoclonal immunoglobulin in them. Compared to multiple myeloma patients, pPCL patients also: exhibit 1) high rates of developing an hypercalcemic crisis, i.e. an potentially life-threatening episode of high ionic calcium (Ca) levels in the blood due to excess bone re-absorption and/or renal failure; b) higher levels of serum lactate dehydrogenase and Beta-2 microglobulin; and c) lower rates of bone but higher rates of soft tissue plasma cell tumors termed plasmacytomas.

Plasma cell leukemia (PCL) is a plasma cell dyscrasia, i.e. a disease involving the malignant degeneration of a subtype of white blood cells called plasma cells. It is the terminal stage and most aggressive form of these dyscrasias, constituting 2% to 4% of all cases of plasma cell malignancies. PCL may present as primary plasma cell leukemia, i.e. in patients without prior history of a plasma cell dyscrasia or as secondary plasma cell dyscrasia, i.e. in patients previously diagnosed with a history of its predecessor dyscrasia, multiple myeloma. The two forms of PCL appear to be at least partially distinct from each other. In all cases, however, PCL is an extremely serious, life-threatening, and therapeutically challenging disease.

Signs and symptoms of WM include weakness, fatigue, weight loss, and chronic oozing of blood from the nose and gums. Peripheral neuropathy occurs in 10% of patients. Enlargement of the lymph nodes, spleen, and/or liver are present in 30–40% of cases. Other possible signs and symptoms include blurring or loss of vision, headache, and (rarely) stroke or coma.

Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs. They develop from bone marrow hematopoietic stem cells and constitute < 0.4% of peripheral blood mononuclear cells (PBMC).

In humans they exhibit plasma cell morphology and express CD4, HLA-DR, CD123, blood-derived dendritic cell antigen-2 (BDCA-2), Toll-like receptor (TLR) 7 and TLR9 within endosomal compartments, but do not express high levels of CD11c or CD14, which distinguishes them from conventional dendritic cells or monocytes, respectively. Mouse pDC express CD11c, B220, BST-2/Tetherin (mPDCA) and Siglec-H and are negative for CD11b.

As components of the innate immune system, these cells express intracellular Toll-like receptors 7 and 9 which detect ssRNA and unmethylated CpG DNA sequences, respectively. Upon stimulation and subsequent activation, these cells produce large amounts (up to 1,000 times more than other cell type) of type I interferon (mainly IFN-α (alpha) and IFN-β (beta)), which are critical pleiotropic anti-viral compounds mediating a wide range of effects.

The number of circulating pDCs are found to be decreased during chronic HIV infection as well as HCV infection.

The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen.

Gene expression profiling has revealed that diffuse large B-cell lymphoma (DLBCL) is composed of at least 3 different sub-groups, each having distinct oncogenic mechanisms that respond to therapies in different ways. Germinal Center B-Cell like (GCB) DLBCLs appear to arise from normal germinal center B cells, while Activated B-cell like (ABC) DLBCLs are thought to arise from postgerminal center B cells that are arrested during plasmacytic differentiation. The differences in gene expression between GCB DLBCL and ABC DLBCL are as vast as the differences between distinct types of leukemia, but these conditions have historically been grouped together and treated as the same disease.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that features a persistent neutrophilia in peripheral blood, myeloid hyperplasia in bone marrow, hepatosplenomegaly, and the absence of the Philadelphia chromosome or a BCR/ABL fusion gene.

Due to the systemic nature of this disease, neoplastic cells can be found in lymph nodes, liver, spleen, skin, and bone marrow.

Patients with this disease usually present at an advanced stage and show systemic involvement. The clinical findings typically include a pruritic skin rash and possibly edema, ascites, pleural effusions, and arthritis.

Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia. These former symptoms are due to release of a substance called histamine from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly is characteristic. The mast cells release also many anticoagulants like heparin which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.

All people with ALPS have signs of lymphoproliferation, which makes it the most common clinical manifestation of the disease. The increased proliferation of lymphoid cells can cause the size of lymphoid organs such as the lymph nodes and spleen to increase (lymphadenopathy and splenomegaly, present in respectively over 90% and over 80% of patients). The liver is enlarged (hepatomegaly in 30 - 40% of patients).

Autoimmune disease is the second most common clinical manifestation and one that most often requires treatment. Autoimmune cytopenias: Most common. Can be mild to very severe. Can be intermittent or chronic. These include: Autoimmune hemolytic anemia, Autoimmune neutropenia, Autoimmune thrombocytopenia.

Other signs can affect organ systems similar to systemic lupus erythematosus (least common, affecting <5% of patients) Symptoms of the nervous system include: Autoimmune cerebellar ataxia; Guillain–Barré syndrome; transverse myelitis. Gastrointestinal signs like Autoimmune esophagitis, gastritis, colitis, hepatitis, pancreatitis can be found or (Dermatologic) Urticaria, (Pulmonary) bronchiolitis obliterans, (Renal) Autoimmune glomerulonephritis, nephrotic syndrome.

Another sign are cancers such as Hodgkin and non-Hodgkin lymphomas which appear to be increased, possibly due to Epstein–Barr virus-encoded RNA-positivity. Some carcinomas may occur. Unaffected family members with genetic mutations are also at an increased risk of developing cancer.

Memory B cells are a B cell sub-type that are formed within germinal centers following primary infection and are important in generating an accelerated and more robust antibody-mediated immune response in the case of re-infection (also known as a "secondary immune response").

Waldenström's macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is a type of cancer affecting two types of B cells, lymphoplasmacytoid cells and plasma cells. Both cell types are white blood cells. WM is characterized by having high levels of a circulating antibody, immunoglobulin M (IgM), which is made and secreted by the cells involved in the disease. WM is an "indolent lymphoma" (i.e., one that tends to grow and spread slowly) and a type of lymphoproliferative disease which shares clinical characteristics with the indolent non-Hodgkin lymphomas. WM is commonly classified as a form of plasma cell dyscrasia. Similar to other plasma cell dyscrasias that, for example, lead to multiple myeloma, WM is commonly preceded by two clinically asymptomatic but progressively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance (i.e. IgM MGUS) and smoldering Waldenström's macroglobulinemia. The WM spectrum of dysplasias differs from other spectrums of plasma cell dyscrasias in that it involves not only aberrant plasma cells but also aberrant lymphoplasmacytoid cells and that it involves IgM while other plasma dyscrasias involve other antibody isoforms.

WM is a rare disease, with only about 1,500 cases per year in the United States. While the disease is incurable, it is treatable. Because of its indolent nature, many patients are able to lead active lives, and when treatment is required, may experience years of symptom-free remission.

Post-transplant lymphoproliferative disorder (PTLD) is the name given to a B-cell proliferation due to therapeutic immunosuppression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia. Some of these B-cells may undergo mutations which will render them malignant, giving rise to a lymphoma.

In some patients, the malignant cell clone can become the dominant proliferating cell type, leading to frank lymphoma, a group of B cell lymphomas occurring in immunosuppressed patients following organ transplant.

Autoimmune lymphoproliferative syndrome (ALPS), also known as Canale-Smith syndrome, is a form of lymphoproliferative disorder (LPDs). It affects lymphocyte apoptosis. It is a RASopathy.

It is a rare genetic disorder of abnormal lymphocyte survival caused by defective Fas mediated apoptosis. Normally, after infectious insult, the immune system down-regulates by increasing Fas expression on activated B and T lymphocytes and Fas-ligand on activated T lymphocytes. Fas and Fas-ligand interact to trigger the caspase cascade, leading to cell apoptosis. Patients with ALPS have a defect in this apoptotic pathway, leading to chronic non-malignant lymphoproliferation, autoimmune disease, and secondary cancers.

Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs "de novo" but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.

People with monoclonal gammopathy generally do not experience signs or symptoms. Some people may experience a rash or nerve problems, such as numbness or tingling. Severe renal disease has also been found in a subset of those with monoclonal gammopathy. MGUS is usually detected by chance when the patient has a blood test for another condition or as part of standard screening.

B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system by secreting antibodies. Additionally, B cells present antigen (they are also classified as professional antigen-presenting cells (APCs)) and secrete cytokines.

In mammals, B cells mature in the bone marrow, which is at the core of most bones. In birds, B cells mature in the bursa of Fabricius, a lymphoid organ. (The "B" from B cells comes from the name of this organ, where it was first discovered by Chang and Glick, and not from bone marrow as commonly believed).

B cells, unlike the other two classes of lymphocytes, T cells and natural killer cells, express B cell receptors (BCRs) on their cell membrane. BCRs allow the B cell to bind a specific antigen, against which it will initiate an antibody response.

Xanthogranulomatous osteomyelitis (XO) is a peculiar aspect of osteomyelitis characterized by prevalent histiocytic infiltrate and foamy macrophage clustering.

Monoclonal gammopathy of undetermined significance (MGUS, "unknown" or "uncertain" may be substituted for "undetermined"), formerly benign monoclonal gammopathy, is a condition in which an abnormal immunoglobin protein (known as a paraprotein) is found in the blood during standard laboratory blood tests. MGUS resembles multiple myeloma and similar diseases, but the levels of antibody are lower, the number of plasma cells (white blood cells that secrete antibodies) in the bone marrow is lower, and it has no symptoms or major problems. However, multiple myeloma develops at the rate of about 1.5% a year, so doctors recommend monitoring it yearly.

The progression from MGUS to multiple myeloma usually involves several steps. In rare cases, it may also be related with a slowly progressive symmetric distal sensorimotor neuropathy.

Macroglobulinemia is the presence of increased levels of macroglobulins in the circulating blood.

It is a plasma cell dyscrasia, resembling leukemia, with cells of lymphocytic, plasmacytic, or intermediate morphology, which secrete a monoclonal immunoglobulin M component. There is diffuse infiltration by the malignant cells of the bone marrow and also, in many cases, of the spleen, liver, or lymph nodes. The circulating macroglobulin can produce symptoms of hyperviscosity syndrome: weakness, fatigue, bleeding disorders, and visual disturbances. Peak incidence of macroglobulinemia is in the sixth and seventh decades of life. (Dorland, 28th ed)

As of 2011 five cases had been reported, involving rib, tibial epiphysis, ulna, distal tibia and femur. Young individuals are prevalently affected but one case involved a 50-year-old woman. Pain, swelling of possibly long duration, fever and increased ESR are some of the main clinical findings. X-ray examination shows lytic foci with sclerotic margins. A neoplastic process can be suspected.

POEMS syndrome (also termed osteosclerotic myeloma, Crow–Fukase syndrome, Takatsuki disease, or PEP syndrome) is a rare paraneoplastic syndrome caused by a clone of aberrant plasma cells. The name POEMS is an acronym for some of the disease's major signs and symptoms (polyneuropathy, organomegaly, endocrinopathy, myeloma protein, and skin changes), as is PEP (polyneuropathy, endocrinopathy, plasma cell dyscrasia).

The signs and symptoms of most neoplasms are due to their mass effects caused by the invasion and destruction of tissues by the neoplasms' cells. Signs and symptoms of a cancer causing a paraneoplastic syndrome result from the release of humoral factors such as hormones, cytokines, or immunoglobulins by the syndrome's neoplastic cells and/or the response of the immune system to the neoplasm. Many of the signs and symptoms in POEMS syndrome are due at least in part to the release of an aberrant immunoglobulin, i.e. a myeloma protein, as well as certain cytokines by the malignant plasma cells.

POEMS syndrome typically begins in middle age – the average age at onset is 50 – and affects up to twice as many men as women.

The disease is an uncontrolled proliferation of B cell lymphocytes latently infected with Epstein-Barr virus. Production of an interleukin-10, an endogenous, pro-regulatory cytokine, has also been implicated.

In immunocompetent patients, Epstein-Barr virus can cause infectious mononucleosis in adolescents, which is otherwise asymptomatic in children during their childhood. However, in immunosuppressed transplant patients, the lack of T-cell immunosurveillance can lead to the proliferation of these EBV-infected of B-lymphocytes.

However, calcineurin inhibitors (tacrolimus and ciclosporin), used as immunosuppressants in organ transplantation inhibit T cell function, and can prevent the control of the B cell proliferation.

Depletion of T cells by use of anti-T cell antibodies in the prevention or treatment of transplant rejection further increases the risk of developing post-transplant lymphoproliferative disorder. Such antibodies include ATG, ALG and OKT3.

Polyclonal PTLD may form tumor masses and present with symptoms due to a mass effect, e.g. symptoms of bowel obstruction. Monoclonal forms of PTLD tend to form a disseminated malignant lymphoma.