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{{B-cell lymphoma}}
{{B-cell lymphoma}}
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==Overview==
It is understood that there are different factors that have important roles in the pathogenesis of B-cell lymphomas including [[reciprocal translocations]] that occur between one of the [[immunoglobulin]] loci and [[proto-oncogene]], the selection for expression of a B-cell receptor (BCR) that promotes survival, increased survival and [[proliferation]] of B-cells mediated by [[antigen]] binding, and [[malignant]] interaction between B-cells and other cells in the tumor microenvironment. [[Chromosomal translocation]]s involving the immunoglobulin heavy locus (IGH@) is a classic cytogenetic abnormality for many B-cell lymphomas, including [[follicular lymphoma]], [[mantle cell lymphoma]], [[diffuse large B cell lymphoma]], [[MALT lymphoma]], [[lymphoplasmacytoid lymphoma]], [[multiple myeloma]], and [[Burkitt's lymphoma]].  


==Pathophysiology==
==Pathophysiology==
===Microscopic Pathology===
===Physiology===
Shown below is a microscopic image of Hodgkins Lymphoma which is a type of B cell lymphoma.Lymph node FNA specimen(Field's stain)
The normal physiology of B-cells can be understood as follows:
The micrograph shows a mixture of cells commonly seen in Hodgkins lymphoma:
*Development of mature B-cells include:
*Eosinophils
**B-cells develop from hematopoietic stem cells originating from bone marrow. [[B-cell]] development occurs in the bone marrow through several steps including the ordered rearrangement of [[IGH@|Ig H] and L chain loci (i.e., [[VDJ recombination]]), positive selection, and negative selection.<ref name="pmid18725575">{{cite journal |vauthors=LeBien TW, Tedder TF |title=B lymphocytes: how they develop and function |journal=Blood |volume=112 |issue=5 |pages=1570–80 |date=September 2008 |pmid=18725575 |pmc=2518873 |doi=10.1182/blood-2008-02-078071 |url=}}</ref>
*Reed Sternberg cells
**B-cell surface consists of membrane-bound Ig, complement component receptors, Fc receptors, and B cell-specific cell surface molecules representing by CDs (i.e., CD19, CD20, CD21, etc.).
*Plasma cells
**Immature (transitional) B-cells migrate from the bone marrow to secondary lymphoid organs (i.e., lymph nodes, spleen) for activation. Activation begins with either T-cell dependent or T-cell independent. T-cell-dependent B-cell activation begins with the binding of the B-cell receptor (BCR) to the T-cell-dependent antigen. T-cell independent B-cell activation begins with BCR crosslinking through polysaccharides or via BCR and toll-like receptor (TLR) costimulation. Following the activation, further maturation steps including [[germinal center]] reaction (i.e., clonal expansion, class switch recombination, [[somatic hypermutation]], affinity maturation) occur.<ref name="pmid23979161">{{cite journal |vauthors=Hess C, Winkler A, Lorenz AK, Holecska V, Blanchard V, Eiglmeier S, Schoen AL, Bitterling J, Stoehr AD, Petzold D, Schommartz T, Mertes MM, Schoen CT, Tiburzy B, Herrmann A, Köhl J, Manz RA, Madaio MP, Berger M, Wardemann H, Ehlers M |title=T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies |journal=J Clin Invest |volume=123 |issue=9 |pages=3788–96 |date=September 2013 |pmid=23979161 |pmc=3754242 |doi=10.1172/JCI65938 |url=}}</ref><ref name="pmid18725575">{{cite journal |vauthors=LeBien TW, Tedder TF |title=B lymphocytes: how they develop and function |journal=Blood |volume=112 |issue=5 |pages=1570–80 |date=September 2008 |pmid=18725575 |pmc=2518873 |doi=10.1182/blood-2008-02-078071 |url=}}</ref>
*Histiocytes
**B-cells can be divided into 3 main types include: B1 B-lymphoctes (originates from fetal liver), marginal zone (MZ) B2 B-lymphocyes, and follicular (FO) B2 B-lymphocytes.<ref name="pmid26700440">{{cite journal |vauthors=Hoffman W, Lakkis FG, Chalasani G |title=B Cells, Antibodies, and More |journal=Clin J Am Soc Nephrol |volume=11 |issue=1 |pages=137–54 |date=January 2016 |pmid=26700440 |pmc=4702236 |doi=10.2215/CJN.09430915 |url=}}</ref>
**B-cells complete their maturation by differention into memory B cells or antibody-secreting plasma cells.
*Functions of B-cells include:<ref name="pmid18725575">{{cite journal |vauthors=LeBien TW, Tedder TF |title=B lymphocytes: how they develop and function |journal=Blood |volume=112 |issue=5 |pages=1570–80 |date=September 2008 |pmid=18725575 |pmc=2518873 |doi=10.1182/blood-2008-02-078071 |url=}}</ref>
**[[Antibody]] production
**Production of [[cytokines]] (i.e. IFN-γ, IL-6, IL-10)
**[[Lymphoid tissue]] organogenesis
**[[Wound healing]]
**Tumor immunity
**[[Transplant rejection]]
**[[Dentritic cell]] regulation
**TH1/TH2 cytokine balance
**Antigen presentation
**Co-stimulation


[[Image:800px-Hodgkin_lymphoma_cytology_large.jpg‎|200px]]
===Pathogenesis===
It is understood that there are different factors that have important roles in the pathogenesis of B-cell lymphomas including:<ref name="pmid15803153">{{cite journal |vauthors=Küppers R |title=Mechanisms of B-cell lymphoma pathogenesis |journal=Nat Rev Cancer |volume=5 |issue=4 |pages=251–62 |date=April 2005 |pmid=15803153 |doi=10.1038/nrc1589 |url=}}</ref>
*[[Reciprocal translocations]] that occur between one of the [[immunoglobulin]] loci and [[proto-oncogene]]
*The selection for expression of a B-cell receptor (BCR) that promotes survival
*Increased survival and [[proliferation]] of B-cells mediated by [[antigen]] binding
*[[Malignant]] interaction between B-cells and other cells in the tumor microenvironment
 
==Genetics==
[[Chromosomal translocation]]s involving the immunoglobulin heavy locus (IGH@) is a classic cytogenetic abnormality for many B-cell lymphomas, including [[follicular lymphoma]], [[mantle cell lymphoma]], [[diffuse large B cell lymphoma]], [[MALT lymphoma]], [[lymphoplasmacytoid lymphoma]], [[multiple myeloma]], and [[Burkitt's lymphoma]]. In these cases, the immunoglobulin heavy locus forms a [[fusion protein]] with another protein that has pro-proliferative or anti-apoptotic abilities. The enhancer element of the immunoglobulin heavy locus, which normally functions to make B cells produce massive production of antibodies, now induces massive transcription of the fusion protein, resulting in excessive pro-proliferative or anti-apoptotic effects on the B cells containing the fusion protein. [[Chromosomal translocation]]s and mutations of [[tumor suppressor genes]] that are associated with B-cell lymphomas include:<ref name="pmid15803153">{{cite journal |vauthors=Küppers R |title=Mechanisms of B-cell lymphoma pathogenesis |journal=Nat Rev Cancer |volume=5 |issue=4 |pages=251–62 |date=April 2005 |pmid=15803153 |doi=10.1038/nrc1589 |url=}}</ref>
*[[Burkitt's lymphoma]] is characterized by the chromosomal translocations between [[MYC]] and either [[IGH@]] or [[IGL@]]. Mutations of [[tumor suppressor genes]] causing Burkitt lymphoma include [[TP53]] and retinoblastoma-like protein 2.
*[[Mantle-cell lymphoma]] is characterized by the chromosomal translocation between [[cyclin D1]] and [[IGH@]]. Mutations of [[tumor suppressor gene]] ATM, is also associated with mantle-cell lymphoma.
*[[Follicular lymphoma]] is characterized by the chromosomal translocation between [[Bcl-2]] and [[IGH@]].
*[[Diffuse large B cell lymphoma]] is characterized by the chromosomal translocations of [[Bcl-2]]–[[IGH@]], [[MYC]]-[[IGH@]], [[MYC]]-[[IGL@]], or the chromosomal translocations involving [[BCL6]]. Mutations of [[tumor suppressor genes]] causing [[diffuse large B cell lymphoma]] include [[CD95]], ATM, and [[TP53]].
*The mutation of [[tumor suppressor gene]] SOCS1 is associated with [[primary mediastinal B-cell lymphoma]].
*[[Classical Hodgkin's lymphoma]] is associated with mutations of tumor suppressor genes including [[IκBα]], IκBe, and [[CD95]].
*Lymphocyte-predominant Hodgkin's lymphoma is characterized by the chromosomal translocations involving [[BCL6]].
*[[MALT lymphoma]] is characterized by the chromosomal translocations of API2–[[MALT1]], [[BCL10]]–[[IGH@]], [[MALT1]]–[[IGH@]], or [[FOXP1]]–[[IGH@]]. The mutation of [[tumor suppressor gene]] [[CD95]] is associated with [[MALT lymphoma]].
*[[Lymphoplasmacytoid lymphoma]] is characterized by the chromosomal translocation between [[PAX5]] and [[IGH@]].
*[[Multiple myeloma]] is characterized by the chromosomal translocations of [[cyclin D1]]–[[IGH@]], [[FGFR3]]–[[IGH@]], or MAF–[[IGH@]]. The mutation of [[tumor suppressor gene]] [[CD95]] is associated with [[multiple myeloma]].
 
==Associated Conditions==
Conditions associated with B-cell lymphoma include:<ref name="pmid15803153">{{cite journal |vauthors=Küppers R |title=Mechanisms of B-cell lymphoma pathogenesis |journal=Nat Rev Cancer |volume=5 |issue=4 |pages=251–62 |date=April 2005 |pmid=15803153 |doi=10.1038/nrc1589 |url=}}</ref>
*Viral infections:
**[[Epstein Barr virus]] (EBV)
**[[Kaposi's sarcoma-associated herpesvirus|HHV8]]
**[[Hepatitis C|Hepatitis C virus]]
*Bacterial infections:
**[[Helicobacter pylori]]
*Autoimmune diseases:
**[[Sjögren's syndrome]]
**[[Rheumatoid arthritis]]
 
==Gross Pathology==
There is no gross pathologic finding characteristic of B-cell lymphoma.
 
==Microscopic Pathology==
Below is a microscopic image of a lymph node [[fine needle aspiration]] (FNA) specimen (Field's stain) of a patient with [[Hodgkin's lymphoma]], a type of B cell lymphoma. The micrograph shows a mixture of cells commonly seen in Hodgkin's lymphoma:
*[[Eosinophils]]
*[[Reed-Sternberg cells]] (hallmark tumor cells of Hodgkin's lymphoma)
*[[Plasma cells]]
*[[Histiocytes]]


===Genetics===
[[Chromosomal translocation]]s involving the [[immunoglobulin heavy locus]] (IGH@) is a classic cytogenetic abnormality for many B-cell lymphomas, including [[follicular lymphoma]], [[mantle cell lymphoma]] and [[Burkitt's lymphoma]]. In these cases, The immunoglobulin heavy locus forms a [[fusion protein]] with another protein that has pro-proliferative or anti-apoptotic abilities. The enhancer element of the immunoglobulin heavy locus, which normally functions to make B cells produce massive production of antibodies, now induces massive transcription of the fusion protein, resulting in excessive pro-proliferative or anti-apoptotic effects on the B cells containing the fusion protein. In [[Burkitt's lymphoma]] and [[mantle cell lymphoma]], the other protein in the fusion is [[c-myc]] (on chromosome 8) and [[cyclin D1]]<ref name=jy>{{cite journal |author=Li JY, Gaillard F, Moreau A, ''et al.'' |title=Detection of translocation t(11;14)(q13;q32) in mantle cell lymphoma by fluorescence in situ hybridization |journal=Am. J. Pathol. |volume=154 |issue=5 |pages=1449–52 |year=1999 |month=May |pmid=10329598 |pmc=1866594 |doi= 10.1016/S0002-9440(10)65399-0|url=}}</ref> (on chromosome 11), respectively, which gives the [[fusion protein]] pro-proliferative ability. In [[follicular lymphoma]], the fused protein is
[[Bcl-2]] (on chromosome 18), which gives the fusion protein anti-apoptotic abilities.


===Video===
===Video===
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Latest revision as of 15:44, 26 January 2022

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2] Shivali Marketkar, M.B.B.S. [3]

Overview

It is understood that there are different factors that have important roles in the pathogenesis of B-cell lymphomas including reciprocal translocations that occur between one of the immunoglobulin loci and proto-oncogene, the selection for expression of a B-cell receptor (BCR) that promotes survival, increased survival and proliferation of B-cells mediated by antigen binding, and malignant interaction between B-cells and other cells in the tumor microenvironment. Chromosomal translocations involving the immunoglobulin heavy locus (IGH@) is a classic cytogenetic abnormality for many B-cell lymphomas, including follicular lymphoma, mantle cell lymphoma, diffuse large B cell lymphoma, MALT lymphoma, lymphoplasmacytoid lymphoma, multiple myeloma, and Burkitt's lymphoma.

Pathophysiology

Physiology

The normal physiology of B-cells can be understood as follows:

  • Development of mature B-cells include:
    • B-cells develop from hematopoietic stem cells originating from bone marrow. B-cell development occurs in the bone marrow through several steps including the ordered rearrangement of [[IGH@|Ig H] and L chain loci (i.e., VDJ recombination), positive selection, and negative selection.[1]
    • B-cell surface consists of membrane-bound Ig, complement component receptors, Fc receptors, and B cell-specific cell surface molecules representing by CDs (i.e., CD19, CD20, CD21, etc.).
    • Immature (transitional) B-cells migrate from the bone marrow to secondary lymphoid organs (i.e., lymph nodes, spleen) for activation. Activation begins with either T-cell dependent or T-cell independent. T-cell-dependent B-cell activation begins with the binding of the B-cell receptor (BCR) to the T-cell-dependent antigen. T-cell independent B-cell activation begins with BCR crosslinking through polysaccharides or via BCR and toll-like receptor (TLR) costimulation. Following the activation, further maturation steps including germinal center reaction (i.e., clonal expansion, class switch recombination, somatic hypermutation, affinity maturation) occur.[2][1]
    • B-cells can be divided into 3 main types include: B1 B-lymphoctes (originates from fetal liver), marginal zone (MZ) B2 B-lymphocyes, and follicular (FO) B2 B-lymphocytes.[3]
    • B-cells complete their maturation by differention into memory B cells or antibody-secreting plasma cells.
  • Functions of B-cells include:[1]

Pathogenesis

It is understood that there are different factors that have important roles in the pathogenesis of B-cell lymphomas including:[4]

Genetics

Chromosomal translocations involving the immunoglobulin heavy locus (IGH@) is a classic cytogenetic abnormality for many B-cell lymphomas, including follicular lymphoma, mantle cell lymphoma, diffuse large B cell lymphoma, MALT lymphoma, lymphoplasmacytoid lymphoma, multiple myeloma, and Burkitt's lymphoma. In these cases, the immunoglobulin heavy locus forms a fusion protein with another protein that has pro-proliferative or anti-apoptotic abilities. The enhancer element of the immunoglobulin heavy locus, which normally functions to make B cells produce massive production of antibodies, now induces massive transcription of the fusion protein, resulting in excessive pro-proliferative or anti-apoptotic effects on the B cells containing the fusion protein. Chromosomal translocations and mutations of tumor suppressor genes that are associated with B-cell lymphomas include:[4]

Associated Conditions

Conditions associated with B-cell lymphoma include:[4]

Gross Pathology

There is no gross pathologic finding characteristic of B-cell lymphoma.

Microscopic Pathology

Below is a microscopic image of a lymph node fine needle aspiration (FNA) specimen (Field's stain) of a patient with Hodgkin's lymphoma, a type of B cell lymphoma. The micrograph shows a mixture of cells commonly seen in Hodgkin's lymphoma:


Video

Shown below is a video of diffuse large B cell lymphoma {{#ev:youtube|9gEo7si6jtc}}

References

  1. ↑ 1.0 1.1 1.2 LeBien TW, Tedder TF (September 2008). "B lymphocytes: how they develop and function". Blood. 112 (5): 1570–80. doi:10.1182/blood-2008-02-078071. PMC 2518873. PMID 18725575.
  2. ↑ Hess C, Winkler A, Lorenz AK, Holecska V, Blanchard V, Eiglmeier S, Schoen AL, Bitterling J, Stoehr AD, Petzold D, Schommartz T, Mertes MM, Schoen CT, Tiburzy B, Herrmann A, Köhl J, Manz RA, Madaio MP, Berger M, Wardemann H, Ehlers M (September 2013). "T cell-independent B cell activation induces immunosuppressive sialylated IgG antibodies". J Clin Invest. 123 (9): 3788–96. doi:10.1172/JCI65938. PMC 3754242. PMID 23979161.
  3. ↑ Hoffman W, Lakkis FG, Chalasani G (January 2016). "B Cells, Antibodies, and More". Clin J Am Soc Nephrol. 11 (1): 137–54. doi:10.2215/CJN.09430915. PMC 4702236. PMID 26700440.
  4. ↑ 4.0 4.1 4.2 Küppers R (April 2005). "Mechanisms of B-cell lymphoma pathogenesis". Nat Rev Cancer. 5 (4): 251–62. doi:10.1038/nrc1589. PMID 15803153.


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