Table of Contents
What does positive for PAX5 mean?
Pax5 immunohistochemistry shows robust nuclear staining, and has become a valuable tool in the diagnosis and subclassification of lymphomas. Pax5 staining is positive in most Hodgkin and B-cell non-Hodgkin lymphomas, and also precursor B-cell lymphoblastic neoplasms.
What is the order of Ig gene rearrangement during B cell development?
Immunoglobulin heavy-chain gene rearrangement begins in early pro-B cells with D to JH joining. This typically occurs at both alleles of the heavy-chain locus, at which point the cell becomes a late pro-B cell. The cell then proceeds to rearrange a VH gene segment to the DJH sequence.
Where do immature B cells develop?
To complete development, immature B cells migrate from the bone marrow into the spleen as transitional B cells, passing through two transitional stages: T1 and T2. Throughout their migration to the spleen and after spleen entry, they are considered T1 B cells. Within the spleen, T1 B cells transition to T2 B cells.
What is classic Hodgkin’s lymphoma?
Classical Hodgkin’s lymphoma is the more common type of this disease. People diagnosed with this type have large lymphoma cells called Reed-Sternberg cells in their lymph nodes. Subtypes of classical Hodgkin’s lymphoma include: Nodular sclerosis Hodgkin’s lymphoma.
What occurs during the second stage of B cell development?
The second stage occurs in the circulation and in peripheral lymphoid tissues; it involves clonal selection of B-lymphocytes by antigens with subsequent proliferation and differentiation to become either memory cells or antibody-producing plasma cells.
Which gene S are turned on and off during B cell development?
Genes encoding proteins required for somatic recombination and receptor expression are turned on and off at set times during B cell development. RAG-1, RAG-2, and TdT are expressed only during the times somatic recombination is occurring: early and late pro-B cell and small pre-B cell stages.
How is B cell differentiation linked with Ig gene rearrangement?
The differentiation of B lymphocytes from their progenitors progresses through a series of successive stages that are defined by sequential rearrangement of Ig loci and surface expression of various stage-specific markers, including Ig heavy and light chain proteins.
What are immature B cells?
Immature B cells are very sensitive to antigen binding, so if they bind self antigen in the bone marrow they die. B cells that do not bind self antigen express d chain and membrane IgD with their IgM about the time they leave the marrow and become mature naive (resting) B cells.
Where do type B lymphocytes develop and mature?
B cell development starts in the bone marrow (BM) and continues in the spleen to final maturation. Developmental progression is guided by sequential events leading to assembly, expression, and signaling of the B cell antigen receptor (BCR).
What are lymphoma B symptoms?
*B symptoms. Fever, drenching night sweats and loss of more than 10 percent of body weight over six months are sometimes termed “B symptoms.” These symptoms are significant to the prognosis and staging of the disease. Some Hodgkin lymphoma symptoms are associated with other, less serious illnesses.
How do memory B cells get activated?
The memory B cells are activated by the variant pathogen to differentiate into long-lived plasma cells or to re-enter the geminal centres (GCs) to replenish the memory B cell pool.
How are memory B cells formed?
Memory B cells are generated in response to T-dependent antigens, during the GC reaction, in parallel to plasma cells (Fig. 2-5). At their exit of GCs, memory B cells acquire migration properties towards extrafollicular areas of the spleen and nodes.
In which stage do B cells start expressing high levels IgD?
T2 transitional B cells
In T2 transitional B cells both IgM and IgD are expressed at high levels, allowing for a high signalling capacity. In this phase, the B cell is not sensitive to negative selection,29,33,42 but protected by antiapoptotic factors.
Which of B cell development does the appearance of complete IgM occur?
B-1 cells secrete predominantly IgM and undergo very little somatic hypermutation. Because they respond to antigens found on multiple pathogens and bind many antigens with low affinity, B-1 cells and their secreted antibodies are called polyreactive. Much of the IgM found in unimmunized mice is produced by B-1 cells.
What is the role of PAX5 in B cells?
Pax5: the guardian of B cell identity and function The transcription factor Pax5 is essential for commitment of lymphoid progenitors to the B lymphocyte lineage. Pax5 fulfils a dual role by repressing B lineage ‘inappropriate’ genes and simultaneously activating B lineage-specific genes.
What are the neoplastic cells found in B-cell lymphoma?
The neoplastic cells are positive for CD20, PAX5, CD10, BCL6 and BCL2 and negative for CD3, CD5, MUM1 and MYC. Ki67 is variable, on average 70%. CD21 is negative. FISH for high grade B cell lymphoma is pending and will be reported in an addendum. A 27 year old man presents with fever, drenching night sweats and supraclavicular lymphadenopathy.
What is the role of transcriptional reprogramming in B cell cycle?
This transcriptional reprogramming restricts the broad signaling capacity of uncommitted progenitors to the B cell pathway, regulates cell adhesion and migration, induces V(H)-DJ(H) recombination, facilitates (pre-)B cell receptor signaling and promotes development to the mature B cell stage.